@article{schwartz_mccrackin_schinazi_hill_vahlenkamp_tompkins_hartmann_2014, title={Antiviral efficacy of nine nucleoside reverse transcriptase inhibitors against feline immunodeficiency virus in feline peripheral blood mononuclear cells}, volume={75}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.75.3.273}, abstractNote={Abstract}, number={3}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Schwartz, Anita M. and McCrackin, Mary Ann and Schinazi, Raymond F. and Hill, Peter B. and Vahlenkamp, Thomas W. and Tompkins, Mary B. and Hartmann, Katrin}, year={2014}, month={Mar}, pages={273–281} }
 @article{miller_petty_tompkins_fogle_2014, title={CD4+CD25+ T regulatory cells activated during feline immunodeficiency virus infection convert T helper cells into functional suppressors through a membrane-bound TGFβ / GARP-mediated mechanism}, volume={11}, ISSN={1743-422X}, url={http://dx.doi.org/10.1186/1743-422X-11-7}, DOI={10.1186/1743-422x-11-7}, abstractNote={We and others have previously reported that cell membrane-bound TGFβ (mTGFβ) on activated T regulatory (Treg) cells mediates suppressor function. Current findings suggest that a novel protein known as Glycoprotein A Repetitions Predominant (GARP) anchors mTGFβ to the Treg cell surface and facilitates suppressor activity. Recently, we have described that GARP+TGFβ+ Treg cells expand during the course of FIV infection. Because Treg cells are anergic and generally exhibit poor proliferative ability, we asked how Treg homeostasis is maintained during the course of feline immunodeficiency virus (FIV) infection. Here, we report that Treg cells from FIV+ cats express GARP and mTGFβ and convert T helper (Th) cells into phenotypic and functional Treg cells. Th to Treg conversion was abrogated by anti-TGFβ or anti-GARP treatment of Treg cells or by anti-TGFβRII treatment of Th cells, suggesting that Treg cell recruitment from the Th pool is mediated by TGFβ/TGFβRII signaling and that cell-surface GARP plays a major role in this process. These findings suggest Th to Treg conversion may initiate a cascade of events that contributes to the maintenance of virus reservoirs, progressive Th cell immunosuppression, and the development of immunodeficiency, all of which are central to the pathogenesis of AIDS lentivirus infections.}, number={1}, journal={Virology Journal}, publisher={Springer Nature}, author={Miller, Michelle M and Petty, Christopher S and Tompkins, Mary B and Fogle, Jonathan E}, year={2014}, pages={7} }
 @article{meng_tompkins_miller_fogle_2014, title={Lentivirus-Activated T Regulatory Cells Suppress T Helper Cell Interleukin-2 Production by Inhibiting Nuclear Factor of Activated T Cells 2 Binding to the Interleukin-2 Promoter}, volume={30}, ISSN={["1931-8405"]}, DOI={10.1089/aid.2013.0062}, abstractNote={Using the feline immunodeficiency virus (FIV) model for AIDS lentivirus infection, we previously demonstrated that Treg cells from FIV-infected cats up-regulate membrane-associated tumor growth factor beta (mTGF-ß) during the course of infection and that activated T lymphocytes up-regulate TGF-ß receptor II (TGF-ßRII) during the course of infection. Furthermore, we have demonstrated that autologous coculture of Tregs with Th cells from FIV-infected cats leads to suppression of interleukin (IL)-2 production and loss of proliferation in a TGF-ß-dependent fashion. Nuclear factor of activated T cells (NFAT) 2 has been identified as integral to effector Th cell maturation and function by promoting IL-2 transcription. Therefore, we questioned whether NFAT2 expression might be altered by TGF-β signaling. Feline NFAT2 exon sequences were identified based upon sequence homology to human and murine NFAT2. Following stimulation, IL-2 and NFAT2 mRNA levels were similarly increased in both FIV(-) and FIV(+) cats. Activated CD4(+)CD25(-) cells from both FIV(-) and FIV(+) cats cocultured with autologous CD4(+)CD25(+) cells or treated with TGF-β demonstrated decreased IL-2 production; however, NFAT2 mRNA levels were unaffected. Although NFAT2 mRNA levels were unaffected, chromatin immunoprecipitation (ChIP) for NFAT2 indicated decreased NFAT2 binding at the IL-2 promoter in suppressed Th cells. These data suggest that TGF-β-mediated Treg cell suppression of IL-2 transcription is modulated through alterations in NFAT2 binding to the IL-2 promoter.}, number={1}, journal={AIDS RESEARCH AND HUMAN RETROVIRUSES}, author={Meng, Liping and Tompkins, Mary and Miller, Michelle and Fogle, Jonathan}, year={2014}, month={Jan}, pages={58–66} }
 @article{miller_fogle_ross_tompkins_2013, title={Feline Glycoprotein A Repetitions Predominant Anchors Transforming Growth Factor Beta on the Surface of Activated CD4(+)CD25(+) Regulatory T Cells and Mediates AIDS Lentivirus-Induced T Cell Immunodeficiency}, volume={29}, ISSN={["1931-8405"]}, DOI={10.1089/aid.2012.0322}, abstractNote={Using the feline immunodeficiency virus (FIV) model for AIDS-lentivirus infection, our laboratory has previously demonstrated that T regulatory (Treg) cell-mediated immune T and B cell dysfunction contributes to lentivirus persistence and chronic disease through membrane bound transforming growth factor beta (mTGFb). Studying Treg cells in the context of infection has been problematic as no inducible marker for activated Treg cells had been identified. However, recent reports in human Treg studies have described a novel protein, glycoprotein A repetitions predominant (GARP), as a unique marker of activated human Treg cells that anchors mTGFb. Herein we extend these studies to the feline Treg system, identifying feline GARP and demonstrating that human and feline GARP proteins are homologous in structure, expression pattern, and ability to form a complex with TGFb. We further demonstrate that GARP and TGFb form a complex on the surface of activated Treg cells and that these GARP(+)TGFb(+) Treg cells are highly efficient suppressor cells. Analysis of expression of this Treg activation marker in the FIV-AIDS model reveals an up-regulation of GARP expressing Treg cells during chronic FIV infection. We demonstrate that the GARP(+) Treg cells from FIV-infected cats suppress T helper cells in vivo and that blocking GARP or TGFb eliminates this suppression. These data suggest that GARP is expressed in complex with TGFb on the surface of activated Treg cells and plays an important role in TGFb(+) Treg-mediated T cell immune suppression during lentivirus infection.}, number={4}, journal={AIDS RESEARCH AND HUMAN RETROVIRUSES}, author={Miller, Michelle M. and Fogle, Jonathan E. and Ross, Peter and Tompkins, Mary B.}, year={2013}, month={Apr}, pages={641–651} }
 @article{miller_fogle_tompkins_2013, title={Infection with Feline Immunodeficiency Virus Directly Activates CD4+ CD25+ T Regulatory Cells}, volume={87}, ISSN={0022-538X}, url={http://dx.doi.org/10.1128/JVI.00996-13}, DOI={10.1128/jvi.00996-13}, abstractNote={ABSTRACT}, number={16}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Miller, M. M. and Fogle, J. E. and Tompkins, M. B.}, year={2013}, month={Jun}, pages={9373–9378} }
 @article{kick_tompkins_flowers_whisnant_almond_2012, title={Effects of stress associated with weaning on the adaptive immune system in pigs}, volume={90}, ISSN={["0021-8812"]}, DOI={10.2527/jas.2010-3470}, abstractNote={This study was designed to investigate the effects of weaning age on specific components of the adaptive immune system in pigs. Twenty-three crossbred pigs were randomly assigned to 1 of 3 treatments: weaning at 14 (14D, n = 8), 21 (21D, n = 7), or 28 (28D, n = 8) d of age. Peripheral blood samples, obtained when pigs were 13, 15, 20, 22, 27, 29, and 35 d of age, were analyzed for peripheral blood cell percentages and concentrations of neutrophils, lymphocytes, T cell subsets, mature B cells, and plasma cortisol concentrations. For each of the 3 groups, weaning increased plasma cortisol concentrations (P < 0.001) and reduced BW percentage change (P < 0.017). Lymphocyte concentrations displayed a treatment effect for the 14D (P = 0.074) and 28D (P = 0.014) groups. Albeit inconsistent, lymphocyte concentrations were less in weaned pigs on the day after weaning than in pigs remaining on the sow or weaned at a younger age. Specifically, mature B cells (CD21(+)) and CD4(+)CD8(+) cells decreased (P < 0.05) after weaning at 28 d of age. Other differences occurred among treatments; however, the differences apparently were not associated with weaning. Based upon the immunological measures used in the present study, there was not an explicit benefit to the adaptive immune system for any weaning age. Early weaning did not negatively affect the adaptive immunological competence of pigs as determined by changes in populations of immune cells.}, number={2}, journal={JOURNAL OF ANIMAL SCIENCE}, author={Kick, A. R. and Tompkins, M. B. and Flowers, W. L. and Whisnant, C. S. and Almond, G. W.}, year={2012}, month={Feb}, pages={649–656} }
 @article{baxter_levy_edinboro_vaden_tompkins_2012, title={Renal Disease in Cats Infected with Feline Immunodeficiency Virus}, volume={26}, ISSN={["0891-6640"]}, DOI={10.1111/j.1939-1676.2011.00871.x}, abstractNote={BackgroundFeline immunodeficiency virus (FIV) and human immunodeficiency virus (HIV) infection cause similar clinical syndromes of immune dysregulation, opportunistic infections, inflammatory diseases, and neoplasia. Renal disease is the 4th most common cause of death associated with HIV infection.}, number={2}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Baxter, K. J. and Levy, J. K. and Edinboro, C. H. and Vaden, S. L. and Tompkins, M. B.}, year={2012}, pages={238–243} }
 @article{cardona_milner_alleman_williams_vernau_breen_tompkins_2011, title={BCR-ABL translocation in a dog with chronic monocytic leukemia}, volume={40}, ISSN={["0275-6382"]}, DOI={10.1111/j.1939-165x.2010.00277.x}, abstractNote={Abstract:A 9‐year‐old female spayed mixed breed dog was evaluated at the University of Florida Small Animal Hospital for marked leukocytosis with no associated clinical signs. CBC abnormalities included marked leukocytosis (106,000/μL), marked monocytosis (78,000/μL), and the presence of 13% blast cells (13,832/μL), supporting a diagnosis of leukemia. Cytopenias and dysplastic changes in other cell lines were not present. Microscopic examination of bone marrow showed hypercellular uniparticles with a marginal increase in frequency of unclassified blast cells (2%), but was otherwise unremarkable. Flow cytometric immunophenotyping of blood cells determined that leukemic cells were CD45+, CD14+, and CD34–, and based on side scatter and CD45 reactivity the marrow contained 19% monoblasts. By immunocytochemical staining, the leukemic cells in the bone marrow were CD11b+, CD11c+, CD11d+, MHC‐II+, MPO+, and CD34–. Fluorescence in situ hybridization (FISH) analysis of peripheral blood leukocytes documented a chromosomal translocation producing a BCR‐ABL gene hybrid, similar to the “Philadelphia” chromosome abnormality recognized in human chronic myelogenous leukemia, as well as a phosphatase and tensin homolog (PTEN) gene deletion. Hydroxyurea therapy was attempted, but was ineffective; the dog died 7 months after initial presentation. Clinical and laboratory findings and the protracted course supported a diagnosis of chronic monocytic leukemia (CMoL) and, to our knowledge, this is the first case of CMoL with a BCR‐ABL chromosomal abnormalitiy described in dogs. This may have clinical implications for treatment of dogs with chronic leukemias associated with particular genetic mutations. However, more case studies are needed to further characterize this disease.}, number={1}, journal={VETERINARY CLINICAL PATHOLOGY}, author={Cardona, Janice A. Cruz and Milner, Rowan and Alleman, A. Rick and Williams, Christina and Vernau, William and Breen, Matthew and Tompkins, Mary}, year={2011}, month={Mar}, pages={40–47} }
 @article{fogle_tompkins_campbell_sumner_tompkins_2011, title={Fozivudine Tidoxil as Single-Agent Therapy Decreases Plasma and Cell-Associated Viremia during Acute Feline Immunodeficiency Virus Infection}, volume={25}, ISSN={["1939-1676"]}, DOI={10.1111/j.1939-1676.2011.0699.x}, abstractNote={Background:  Feline immunodeficiency virus (FIV) is a lentivirus that infects domestic and wild felidae and the course of disease is similar to that of human immunodeficiency virus infection. The thymidine nucleoside analog fozivudine (FZD) tidoxil is a lipid—zidovudine (ZDV) conjugate and member of the family of nucleoside reverse transcriptase (RT) inhibitors (NRTIs).}, number={3}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Fogle, J. E. and Tompkins, W. A. and Campbell, B. and Sumner, D. and Tompkins, M. B.}, year={2011}, pages={413–418} }
 @article{fogle_mexas_tompkins_tompkins_2010, title={CD4(+)CD25(+) T Regulatory Cells Inhibit CD8(+) IFN-gamma Production During Acute and Chronic FIV Infection Utilizing a Membrane TGF-beta-Dependent Mechanism}, volume={26}, ISSN={["1931-8405"]}, DOI={10.1089/aid.2009.0162}, abstractNote={CD8(+) lymphocytes are critical to the control and elimination of viral pathogens. Impaired CD8(+) responses are well recognized in lentiviral infections; however, the mechanisms underlying CD8(+) impairment remain elusive. Using the feline immunodeficiency virus (FIV) model for human AIDS, we reported previously that CD4(+)CD25(+) Treg cells in both the acute and long-term, asymptomatic phase of infection are constitutively activated and suppress CD4(+)CD25(-) T cell responses. In the current study, we have demonstrated that CD4(+)CD25(+) Treg cells suppress CD8(+) responses to immune stimulation during both the acute and chronic, asymptomatic phase of FIV infection and that the mechanism of suppression may be mediated by membrane-associated TGF-beta (mTGF-beta) on CD4(+)CD25(+) lymphocytes. Depletion of CD4(+)CD25(+) lymphocytes from lymph node suspensions significantly enhanced production of IFN-gamma during the acute phase of infection and coculture of CD8(+) lymphocytes with CD4(+)CD25(+) lymphocytes resulted in suppression of CD8(+) IFN-gamma during both the acute and chronic stages of infection. FACS analysis indicated that there was TGF-betaRII upregulation on CD8(+) cells from FIV(+) cats during the acute and chronic stage of infection. In addition, there was upregulation of mTGF-beta on the CD4(+)CD25(+) subset in chronically infected cats. In support of activation of the TGF-beta signaling pathway, Western blotting showed Smad 2 phosphorylation in CD8(+) targets following CD4(+)CD25(+)/CD8(+) coculture. These results demonstrate the suppressive effect CD4(+)CD25(+) Treg cells have on the CD8(+) immune response during the acute and chronic stages of FIV infection and suggest that the mechanism of suppression may be mediated by mTGF-beta.}, number={2}, journal={AIDS RESEARCH AND HUMAN RETROVIRUSES}, author={Fogle, Jonathan E. and Mexas, Angela M. and Tompkins, Wayne A. and Tompkins, Mary B.}, year={2010}, month={Feb}, pages={201–216} }
 @article{fogle_tompkins_tompkins_2010, title={CD4(+)CD25(+) T regulatory cells from FIV+ cats induce a unique anergic profile in CD8(+) lymphocyte targets}, volume={7}, ISSN={["1742-4690"]}, DOI={10.1186/1742-4690-7-97}, abstractNote={Abstract}, journal={RETROVIROLOGY}, author={Fogle, Jonathan E. and Tompkins, Wayne A. and Tompkins, Mary B.}, year={2010}, month={Nov} }
 @article{mexas_fogle_tompkins_tompkins_2008, title={CD4(+)CD25(+) regulatory T cells are infected and activated during acute FIV infection}, volume={126}, ISSN={["1873-2534"]}, DOI={10.1016/j.vetimm.2008.08.003}, abstractNote={HIV-induced AIDS may be mediated by the activation of immunosuppressive CD4+CD25+ T regulatory cells (Treg cells). Treg cells have been shown to regulate CD4+ and CD8+ immune responses to HIV and FIV antigens in vitro. We tested the hypothesis that Treg cells become infected and activated during the acute infection with FIV leading to the suppression of CD4+ T helper cell responses. Cats were experimentally infected with FIV-NCSU1 and blood and lymph node cells were collected at weekly intervals following inoculation. Real-time RT-PCR was used to determine plasma viremia and the relative expression of FIV, FoxP3, TGF-β, and GAPDH mRNA copies in CD4+CD25+ and CD4+CD25− T cell subsets. Flow cytometry was used to assess the absolute numbers of each cell type and the expression of surface TGF-β and intracellular FoxP3 in CD4+CD25+ and CD4+CD25− T cells at each time-point. Treg suppression of IL-2 production in CD4+ T helper cells was assessed by ELISPOT assays. Our results showed that peak viremia occurred at 2 weeks post infection and correlated with maximal infectivity in CD4+CD25+ T cell populations. FIV-gag-mRNA levels were higher in CD4+CD25+ T cells than CD4+CD25− T cells throughout the acute phase of infection. Induction of FoxP3 and TGF-β indicated activation of Treg cells during the acute stage infection, which was confirmed by Treg cell suppression of IL-2 production by CD4+ Th cells in an ELISPOT assay. Our findings support the hypothesis that early activation of Treg immunosuppressor function may limit an effective anti-FIV response, contributing to the establishment of chronic infection and the immunodeficiency caused by this virus.}, number={3-4}, journal={VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY}, author={Mexas, Angela M. and Fogle, Jonathan E. and Tompkins, Wayne A. and Tompkins, Mary B.}, year={2008}, month={Dec}, pages={263–272} }
 @article{hudson_tompkins_meeker_2008, title={Endothelial cell suppression of peripheral blood mononuclear cell trafficking in vitro during acute exposure to feline immunodeficiency virus}, volume={334}, ISSN={["0302-766X"]}, DOI={10.1007/s00441-008-0623-7}, abstractNote={Trafficking of peripheral blood mononuclear cells (PBMCs) into the brain is a critical step in the initiation of human immunodeficiency virus (HIV)-associated central nervous system disease. To examine potential factors that control trafficking during the earliest stages of infection, PBMC transmigration across a cultured feline brain endothelial cell (BECs) monolayer was measured after selective exposure of various cell types to feline immunodeficiency virus (FIV). Infection of the PBMCs with FIV increased the trafficking of monocytes and CD4 and CD8 T cells. Additional exposure of the BECs to FIV suppressed mean monocyte, CD4 T cell, and CD8 T cell trafficking. B cell trafficking was unaltered by these changing conditions. Subsequent exposure of astrocytes or microglia to FIV altered transmigration of different PBMC subsets in different ways. Treated microglia compared with treated astrocytes decreased monocyte transmigration, whereas B cell transmigration was increased significantly. When both astrocytes and microglia were exposed to FIV, an increase in CD8 T cell transmigration relative to BECs alone, to BECs plus astrocytes, or to BECs plus microglia was demonstrated. Thus, initial exposure of PBMCs to FIV is sufficient to induce a general increase in trafficking, whereas initial exposure of endothelial cells to FIV tends to down-regulate this effect. Selectivity of trafficking of specific PBMC subsets is apparent only after exposure of cells of the central nervous system to FIV in co-culture with the endothelium.}, number={1}, journal={CELL AND TISSUE RESEARCH}, author={Hudson, Lola C. and Tompkins, Mary B. and Meeker, Rick B.}, year={2008}, month={Oct}, pages={55–65} }
 @article{smithberg_fogle_mexas_reckling_lankford_tompkins_dean_2008, title={In vivo depletion of CD4(+)CD25(+) regulatory T cells in cats}, volume={329}, ISSN={["0022-1759"]}, DOI={10.1016/j.jim.2007.09.015}, abstractNote={To establish a characterized model of regulatory T cell (Treg) depletion in the cat we assessed the kinetics of depletion and rebound in peripheral and central lymphoid compartments after treatment with anti-CD25 antibody as determined by cell surface markers and FOXP3 mRNA expression. An 82% decrease in circulating CD4+CD25+ Tregs was observed by day 11 after treatment. CD4+CD25+ cells were also reduced in the thymus (69%), secondary lymphoid tissues (66%), and gut (67%). Although CD4+CD25+ cells rebound by day 35 post-treatment, FOXP3 levels remain depressed suggesting anti-CD25 antibody treatment has a sustainable diminutive effect on the Treg population. To determine whether CD25+ Treg depletion strategies also deplete activated CD25+ effector cells, cats were immunized with feline immunodeficiency virus (FIV) p24-GST recombinant protein, allowing them to develop a measurable memory response, prior to depletion with anti-CD25 antibody. Anti-FIV p24-GST effector cell activity in peripheral blood after depletion was sustained as determined by antigen-specific T cell proliferation and humoral responses against FIV p24-GST with an ELISA for antigen-specific feline IgG. Furthermore, development of an anti-mouse response in Treg-depleted cats was similar to control levels indicating the retained capacity to respond to a novel antigen. We conclude that despite alterations in CD25+ cell levels during depletion, the feline immune system remains functional. We demonstrate here a model for the study of disease pathogenesis in the context of reduced numbers of immunosuppressive CD4+CD25+ Tregs throughout the feline immune system.}, number={1-2}, journal={JOURNAL OF IMMUNOLOGICAL METHODS}, author={Smithberg, S. Rochelle and Fogle, Jonathan E. and Mexas, Angela M. and Reckling, Stacie K. and Lankford, Susan M. and Tompkins, Mary B. and Dean, Gregg A.}, year={2008}, month={Jan}, pages={81–91} }
 @article{tompkins_tompkins_2008, title={Lentivirus-induced immune dysregulation}, volume={123}, ISSN={["0165-2427"]}, DOI={10.1016/j.vetimm.2008.01.011}, abstractNote={FIV/HIV infections are associated with an early robust humoral and cellular anti-viral immune response followed by a progressive immune suppression that eventually results in AIDS. Several mechanisms responsible for this immune dysfunction have been proposed including cytokine dysregulation, immunologic anergy and apoptosis, and inappropriate activation of immune regulatory cells. Studies on FIV infection provide evidence for all three. Cytokine alterations include decreases in IL2 and IL12 production and increases in IFNgamma and IL10 in FIV(+) cats compared to normal cats. The elevated IL10:IL12 ratio is associated with the inability of FIV(+) cats to mount a successful immune response to secondary pathogens. Additionally, chronic antigenic (FIV) stimulation results in an increase in the percent of activated T cells expressing B7 and CTLA4 co-stimulatory molecules in infected cats. The expression of these molecules is associated with T cells that are undergoing apoptosis in the lymph nodes. As ligation of CTLA4 by B7 transduces a signal for induction of anergy, one can speculate that the activated T cells are capable of T cell-T cell interactions resulting in anergy and apoptosis. The inability of CD4(+) cells from FIV(+) cats to produce IL2 in response to recall antigens and the gradual loss of CD4(+) cell numbers could be due to B7-CTLA4 interactions. The chronic antigenemia may also lead to activation of CD4(+)CD25(+) T regulatory cells. Treg cells from FIV(+) cats are chronically activated and inhibit the mitogen-induced proliferative response of CD4(+)CD25(-) by down-regulating IL2 production. Although Treg cell activation can be antigen-specific, the suppressor function is not, and thus activated Treg cells would suppress responses to secondary pathogens as well as to FIV. Concomitant with the well-known virus-induced immune suppression is a progressive immune hyper-activation. Evidence for immune hyper-activation includes polyclonal B cell responses, gradual replacement of naïve CD4(+) and CD8(+) T cell phenotypes with activation phenotypes (CD62L(-), B7(+), CTLA4(+)), and the chronic activation of CD4(+)CD25(+) Treg cells. Thus lentivirus infections lead to severe immune dysregulation manifested as both chronic immune suppression and chronic immune activation. FIV infection of cats provides a number of advantages over other lentivirus infections as a model to study this immune dysregulation. It is a natural infection that has existed in balance with the cat's immune system for thousands of years. As such, the natural history and pathogenesis provides an excellent model to study the long-term relationships between AIDS lentivirus and host immune system function/dysregulation.}, number={1-2}, journal={VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY}, author={Tompkins, Mary B. and Tompkins, Wayne A.}, year={2008}, month={May}, pages={45–55} }
 @article{petty_tompkins_tompkins_2008, title={Transforming growth factor-beta/transforming growth factor-beta RII signaling may regulate CD4(+)CD25(+) T-regulatory cell homeostasis and suppressor function in feline AIDS lentivirus infection}, volume={47}, ISSN={["1525-4135"]}, DOI={10.1097/QAI.0b013e318160df70}, abstractNote={We have reported that CD4+CD25+ T-regulatory (Treg) cells are fully activated for suppressor function in feline immunodeficiency virus (FIV)-infected cats. Studies have suggested that surface transforming growth factor-β (TGFβ; membrane TGFβ [mTGFβ]) is a feature of activated CD4+CD25+ Treg cells and may play a role in Treg homeostasis and suppressor function. Herein, we explore the role of TGFβ in feline Treg homeostasis and suppressor function and what effect FIV infection of cats might have on these processes. Stimulation of CD4+CD25− T helper (Th) cells with Concanavalin A (ConA) plus TGFβ converts them to Treg-like cells capable of suppressor function. Reverse-transcription polymerase chain reaction and flow cytometry revealed that these ConA/TGFβ-converted Treg cells upregulate Foxp3 and mTGFβ. ConA stimulation of CD4+CD25− T cells upregulates TGFβ receptor II (RII), and pretreatment of these cells with anti-TGFβ-RII antibodies blocks the TGFβ-induced conversion to Treg cells. Pretreatment of ConA/TGFβ-converted Treg cells with anti-TGFβ antibodies also abrogates their suppressor function, suggesting that Treg homeostasis and suppressor function may be mediated by mTGFβ. Finally, we show that treatment of CD4+CD25+ mTGFβ-positive Treg cells from FIV-infected cats with anti-TGFβ antibodies or treatment of ConA-stimulated CD4+CD25− Th target cells with anti-TGFβ-RII antibodies diminishes suppressor function. These data suggest that the recruitment of Treg cells from the Th pool and suppressor function of Treg cells are dependent on the TGFβ/TGFβ-RII signaling pathway and that this pathway is constitutively upregulated in asymptomatic chronically FIV-infected cats.}, number={2}, journal={JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES}, author={Petty, Christopher S. and Tompkins, Mary B. and Tompkins, Wayne A.}, year={2008}, month={Feb}, pages={148–160} }
 @article{liu_hudson_tompkins_vahlenkamp_colby_rundle_meeker_2006, title={Cerebrospinal fluid is an efficient route for establishing brain infection with feline immunodeficiency virus and transfering infectious virus to the periphery}, volume={12}, ISSN={["1538-2443"]}, DOI={10.1080/13550280600889567}, abstractNote={Like human immunodeficiency virus (HIV), feline immunodeficiency virus (FIV) invades and infects the central nervous system (CNS) soon after peripheral infection. The appearance of viral RNA is particularly prominent in the cerebrospinal fluid (CSF), suggesting an efficient route of virus transfer across the blood-CSF barrier. This raises the concern whether this route can establish a stable viral reservoir and also be a source of virus capable of reseeding peripheral systems. To examine this possibility, 200 μl of cell-free NCSU1 FIV or FIV-infected choroid plexus macrophages (ChP-Mac) was directly injected into the right lateral ventricle of the brain. Negative controls were sham inoculated with uninfected ChP-Mac or virus-free culture supernatant and positive controls were infected systemically by intraperitoneal (i.p.) injection. Intracerebroventricular (i.c.v.) inoculation with cell-free FIV resulted in high levels of plasma FIV RNA detected as early as 1 to 2 weeks post inoculation in all cats. In each case, the plasma viremia preceded the detection of CSF viral RNA. Compared to i.p. cats, i.c.v. cats had 32-fold higher CSF viral loads, 8-fold higher ratios of CSF to plasma viral load, and a 23-fold greater content of FIV proviral DNA in the brain. No FIV RNA was detected in plasma or CSF from the cats inoculated with FIV-infected ChP-Mac but an acute inflammatory response and a slight suppression of the CD4+:CD8+ ratio were observed. These results indicate that free FIV circulating in the CSF promotes infection of the CNS and provides a highly efficient pathway for the transfer of infectious virus to the periphery.}, number={4}, journal={JOURNAL OF NEUROVIROLOGY}, author={Liu, Pinghuang and Hudson, Lola C. and Tompkins, Mary B. and Vahlenkamp, Thomas W. and Colby, Brenda and Rundle, Cyndi and Meeker, Rick B.}, year={2006}, month={Aug}, pages={294–306} }
 @article{liu_hudson_tompkins_vahlenkamp_meeker_2006, title={Compartmentalization and evolution of feline immunodeficiency virus between the central nervous system and periphery following intracerebroventricular or systemic inoculation}, volume={12}, ISSN={["1355-0284"]}, DOI={10.1080/13550280600889575}, abstractNote={The emergence of distinct neuropathogenic strains resulting from the adaptation and the unique evolution of human immunodeficiency virus (HIV) in the brain may contribute to the development of HIV-induced neurological diseases. In this study, the authors tracked early changes in virus evolution and compartmentalization between peripheral tissues and the central nervous system (CNS) after intracerebroventricular (i.c.v.) or intraperitoneal (i.p.) inoculation of animals with cell-free feline immunodeficiency virus (FIV). Using the FIV-NCSU1 envelope V3–V4 heteroduplex tracking assay (HTA), the authors observed a rapid compartmentalization of envelope variants between the CNS and periphery. Animals receiving the i.c.v. inoculation showed two peaks of viral RNA in the cerebrospinal fluid (CSF) with very different HTA patterns. Compared to the initial viral peak in CSF, the second peak showed an increased compartmentalization from plasma, reduced viral diversity, and more divergence from the proviral DNA in peripheral blood mononuclear cells (PBMCs) and the choroid plexus. In contrast, changes in plasma over the same time period were small. Different animals harbored different FIV DNA genotypes with varied regional compartmentalization within the brain. These results demonstrated that the virus within the CNS experienced a relatively independent but variable evolution from the periphery. Initial penetration of virus into the CSF facilitated the development of brain-specific reservoirs and viral diversification within the CNS.}, number={4}, journal={JOURNAL OF NEUROVIROLOGY}, author={Liu, Pinghuang and Hudson, Lola C. and Tompkins, Mary B. and Vahlenkamp, Thomas W. and Meeker, Rick B.}, year={2006}, month={Aug}, pages={307–321} }
 @article{hudson_bragg_tompkins_meeker_2005, title={Astrocytes and microglia differentially regulate trafficking of lymphocyte subsets across brain endothelial cells}, volume={1058}, ISSN={["1872-6240"]}, DOI={10.1016/j.brainres.2005.07.071}, abstractNote={Feline brain endothelial cells (BECs), astrocytes, and microglia were combined in different configurations in a cell culture insert system to assess the effect of different cell types on the trafficking of peripheral blood mononuclear cell (PBMC) subsets in response to feline immunodeficiency virus (FIV). The addition of astrocytes to BECs significantly increased the adherence of PBMCs. This increase in adherence was suppressed by microglia, whereas microglia alone had no effect on PBMC adherence. FIV exposure of the glial cells did not alter PBMC adherence as compared to same configurations with untreated cells. All PBMC subsets showed some level of trafficking across the endothelial cell layer. The level of trafficking of monocytes and B cells was significantly increased if astrocytes were present. The presence of microglia with the astrocytes reduced transmigration across all PBMC subsets. FIV exposure of astrocytes significantly increased the percentage of CD8 T cell transmigration from 24% to 64% of the total CD4 and CD8 numbers. The presence of microglia significantly reversed the preferential trafficking of CD8 cells in the presence of astrocytes. The results suggested that interaction between the triad of endothelial cells, astrocytes, and microglia played an important, but varying, role in the trafficking of different PBMC subsets. In general, astrocytes had a positive effect on trafficking of PBMCs, while microglia had a suppressive effect. Effects of FIV on trafficking were largely restricted to increases seen in CD8 T cells and monocytes.}, number={1-2}, journal={BRAIN RESEARCH}, author={Hudson, LC and Bragg, DC and Tompkins, MB and Meeker, RB}, year={2005}, month={Oct}, pages={148–160} }
 @article{joshi_garg_tompkins_tompkins_2005, title={Different thresholds of T cell activation regulate FIV infection of CD4(+)CD25(+) and CD4(+)CD25(-) cells}, volume={335}, ISSN={["0042-6822"]}, DOI={10.1016/j.virol.2005.02.016}, abstractNote={Cellular activation plays an important role in retroviral replication. Previously, we have shown that CD4+CD25+ T cells by the virtue of their partially activated phenotype represent ideal candidates for a productive feline immunodeficiency virus (FIV) infection. In the present study, we extended our previous observations with regard to FIV replication in CD4+CD25+ and CD4+CD25− cells under different stimulation conditions. Both CD4+CD25+ and CD4+CD25− cells remain latently infected in the absence of IL-2 or concanvalinA (ConA), respectively; harboring a replication competent provirus capable of reactivation several days post-infection. While CD4+CD25+ cells require low levels of exogenous IL-2 and virus inputs for an efficient FIV replication, CD4+CD25− T cells can only be productively infected in the presence of either high concentrations of IL-2 or high virus titers, even in the absence of mitogenic stimulation. Interestingly, while high virus input activates CD4+CD25− cells to replicate FIV, it induces apoptosis in a high percentage of CD4+CD25+ T cells. High IL-2 concentrations but not high virus inputs lead to surface upregulation of CD25 and significant cellular proliferation in CD4+CD25− cells. These results suggest that CD4+CD25+ and CD4+CD25− T cells have different activation requirements which can be modulated by both viral and cytokine stimuli to reach threshold activation levels in order to harbor a productive FIV infection. This holds implications in vivo for CD4+CD25+ and CD4+CD25− cells to serve as potential reservoirs of a productive and latent FIV infection.}, number={2}, journal={VIROLOGY}, author={Joshi, A and Garg, H and Tompkins, MB and Tompkins, WA}, year={2005}, month={May}, pages={212–221} }
 @article{joshi_garg_tompkins_tompkins_2005, title={Preferential feline immunodeficiency virus (FIV) infection of CD4(+) CD25(+) T-regulatory cells correlates both with surface expression of CXCR4 and activation of FIV long terminal repeat binding cellular transcriptional factors}, volume={79}, ISSN={["0022-538X"]}, DOI={10.1128/JVI.79.8.4965-4976.2005}, abstractNote={ABSTRACT}, number={8}, journal={JOURNAL OF VIROLOGY}, author={Joshi, A and Garg, H and Tompkins, MB and Tompkins, WA}, year={2005}, month={Apr}, pages={4965–4976} }
 @article{vahlenkamp_tompkins_tompkins_2005, title={The role of CD4(+)CD25(+) regulatory T cells in viral infections}, volume={108}, ISSN={["1873-2534"]}, DOI={10.1016/j.vetimm.2005.07.011}, abstractNote={Many virus infections result in the suppression of one or more functions of the immune system. Multiple mechanisms have been proposed to explain viral-induced immunosuppression, including an imbalance in the cellular Th1/Th2 or cytokine profile, induction of anergy, depletion of effector cells and most recently the activation of CD4+CD25+ regulatory T (T reg) cells. CD4+CD25+ T reg cells are a subset of circulating CD4+ T cells with suppressive properties. CD4+CD25+ T reg cells were first identified in mice as cells capable of maintaining self-tolerance by suppressing autoreactive T cells. This review focuses on interactions between CD4+CD25+ T reg cells and viral pathogens. Most cases in which CD4+CD25+ T reg cells participate in response to infection reported so far involve chronic or persistent viral infections. Examples have been growing recently and include members of different viral families including retroviridae, herpesviridae and picornaviridae. It is currently not known how microbes are recognized by CD4+CD25+ T reg cells and whether exoantigen-specific T reg cells are of the same lineage as self-reacting natural T reg cells or represent peripherally induced counterparts derived from CD4+CD25− T cells. The findings that T reg cells influence the functional immunity during viral infections, however, might indicate that, in some cases, virus-specific T reg cells not only influence immune pathology or prevent pathogen elimination but also can promote a generalized state of immunosuppression in vivo such that the host is more susceptible to secondary infections with other pathogens or has reduced resistance to tumors. Conceivably, the activities of T reg cells might be one of the contributing reasons why it has been difficult so far to produce effective vaccines against some persisting viral infections.}, number={1-2}, journal={VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY}, author={Vahlenkamp, TW and Tompkins, MB and Tompkins, WAF}, year={2005}, month={Oct}, pages={219–225} }
 @article{smith_tompkins_breitschwerdt_2004, title={Antinuclear antibodies can be detected in dog sera reactive to Bartonella vinsonii subsp berkhoffii, Ehrlichia canis, or Leishmania infantum antigens}, volume={18}, ISSN={["1939-1676"]}, DOI={10.1892/0891-6640(2004)18<47:AACBDI>2.0.CO;2}, abstractNote={The presence of antinuclear antibodies (ANAs) is used to support a clinical diagnosis of systemic lupus erythematosus (SLE) in dogs. However, clinicians must interpret the detection of ANAs with caution, particularly in light of increasing evidence that dogs with known bacterial and protozoal infections can have high ANA titers. Retrospectively, medical records were reviewed for all dogs that were concurrently tested for antinuclear antigens and Bartonella vinsonii (berkhoffii), Ehrlichia canis, or Rickettsia rickettsii antigens between 1990 and 2000. When analyzed on the basis of reactivity to a specific infectious agent, 75% of the B vinsonii (berkhoffii) seroreactors, 16.7% of the E canis seroreactors, and 0% of the R rickettsii seroreactors had concurrent ANAs. Subsequent prospective testing did not detect ANAs in convalescent sera from dogs experimentally infected with B vinsonii (berkhoffii), E canis, or R rickettsii. However, 10-20% B vinsonii (berkhoffii), E canis, or Leishmania infantum reactive sera from naturally infected dogs contained ANAs. In addition, 45% of sera from dogs that are reactive to multiple vectorborne organisms were more likely to contain ANAs when compared to sera from dogs reactive to only 1 test antigen. When interpreting the relevance of seroreactivity to nuclear antigens, clinicians should recognize that dogs with seroreactivity to B vinsonii (berkhoffii), E canis, or L infantum antigens (especially those with seroreactivity to more than one of these pathogens) may produce ANAs.}, number={1}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Smith, BE and Tompkins, MB and Breitschwerdt, EB}, year={2004}, pages={47–51} }
 @article{vahlenkamp_bull_dow_collisson_winslow_phadke_tompkins_tompkins_2004, title={B7(+)CTLA4(+) T cells engage in T-T cell interactions that mediate apoptosis: a model for lentivirus-induced T cell depletion}, volume={98}, ISSN={["0165-2427"]}, DOI={10.1016/j.vetimm.2003.12.006}, abstractNote={Apoptosis in lymph node (LN) T cells of feline immunodeficiency virus (FIV)-infected cats is associated with cells co-expressing B7.1 and B7.2 costimulatory molecules, and their ligand CTLA4. To study the possibility of B7.1/B7.2-CTLA4 mediated T-T interactions and the predicted induction of T cell apoptosis in vitro, costimulatory molecules were up-regulated on CD4+ and CD8+ T cells by mitogen stimulation. B7.1 expression on in vitro stimulated CD4+ and CD8+ cells increased within 24h; B7.2 and CTLA4 expression increased after 48-72 h. Apoptosis, as analyzed by terminal deoxynucleotidyl transferase (transferase nick end labeling, TUNEL)-based staining followed by three color flow cytometric analysis, correlated to the cells expressing B7 and/or CTLA4. Blocking experiments revealed that CD4+ and CD8+ T cell apoptosis could be significantly inhibited with anti-B7 antibodies. As FIV infection results in immune activation with a T cell phenotype similar to that of the in vitro activated T cells, the data support the hypothesis that the chronic expansion of B7+CTLA4+ LN T cells in infected cats allows for T-T cell interactions resulting in T cell depletion and eventually the development of AIDS.}, number={3-4}, journal={VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY}, author={Vahlenkamp, TW and Bull, ME and Dow, JL and Collisson, EW and Winslow, BJ and Phadke, AP and Tompkins, WAF and Tompkins, MB}, year={2004}, month={Apr}, pages={203–214} }
 @article{levy_liang_ritchey_davidson_tompkins_tompkins_2004, title={Failure of FIV-infected cats to control Toxoplasma gondii correlates with reduced IL2, IL6, and IL12 and elevated IL10 expression by lymph node T cells}, volume={98}, ISSN={["0165-2427"]}, DOI={10.1016/j.vetimm.2003.11.002}, abstractNote={Increased susceptibility to intracellular pathogens in HIV-infected individuals and FIV-infected cats is attributed to a defective T-helper 1 (Th1) immune response. However, little is known about specific cytokine responses to secondary pathogens. To address this question, control and FIV-infected cats were challenged with Toxoplasma gondii, and lymph node cells analyzed for cytokine mRNA expression. Twenty-four weeks post-FIV infection, prior to T. gondii challenge, IL2 and IL12 mRNAs were depressed, whereas IL10 and IFNγ mRNAs were increased in CD4+ and CD8+ subsets. Following T. gondii challenge, control cats showed increased expression of IL2, IFNγ, IL10, IL12, and IL6 mRNAs. In contrast, IL2, IL6, IFNγ, and IL12 mRNAs were suppressed in FIV–T. gondii co-infected cats, whereas IL10 remained at the high prechallenge levels. IFNγ and IL10 mRNAs were produced by both CD4+ and CD8+ cells in FIV–T. gondii cats. Elevated IL10 may suppress a Th1 cytokine response to T. gondii challenge.}, number={1-2}, journal={VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY}, author={Levy, JK and Liang, YH and Ritchey, JW and Davidson, MG and Tompkins, WA and Tompkins, MB}, year={2004}, month={Mar}, pages={101–111} }
 @article{vahlenkamp_tompkins_tompkins_2004, title={Feline immunodeficiency virus infection phenotypically and functionally activates immunosuppressive CD4(+)CD25(+) T regulatory cells}, volume={172}, ISSN={["1550-6606"]}, DOI={10.4049/jimmunol.172.8.4752}, abstractNote={Abstract}, number={8}, journal={JOURNAL OF IMMUNOLOGY}, author={Vahlenkamp, TW and Tompkins, MB and Tompkins, WAF}, year={2004}, month={Apr}, pages={4752–4761} }
 @article{joshi_vahlenkamp_garg_tompkins_tompkins_2004, title={Preferential replication of FIV in activated CD4(+)CD25(+)T cells independent of cellular proliferation}, volume={321}, ISSN={["0042-6822"]}, DOI={10.1016/j.virol.2004.01.014}, abstractNote={Studies attempting to identify reservoirs of HIV-1 latency have documented that the virus persists as both a latent and productive infection in subsets of CD4+ cells. Reports regarding establishment of a stable HIV-1 infection in quiescent T cells in vitro, however, are controversial. In the present study, we investigated the susceptibility of naive and activated CD4+ cell subsets (distinguished by differential expression of CD25) to feline immunodeficiency virus (FIV) infection, their ability to replicate the virus, and potentially act as a reservoir for virus persistence in infected animals. While both CD4+CD25+ and CD4+CD25− cells are susceptible to FIV infection in vitro and in vivo, only CD4+CD25+ cells produce infectious virions when cultured with interleukin-2 (IL-2). Latently infected CD4+CD25− cells produce infectious virions following ConcanvalinA (ConA) stimulation, which correlates with upregulated surface expression of CD25. In contrast to CD4+CD25− cells, CD4+CD25+ cells remain unresponsive to mitogen stimulation and are relatively resistant to apoptosis whether or not infected with FIV. The ability of CD4+CD25+ cells to replicate FIV efficiently in the presence of IL-2 but remain anergic and unresponsive to apoptotic signaling suggests that these cells may provide a reservoir of productive FIV infection. On the contrary, CD4+CD25− cells seem to establish as latent viral reservoirs capable of being reactivated after stimulation.}, number={2}, journal={VIROLOGY}, author={Joshi, A and Vahlenkamp, TW and Garg, H and Tompkins, WAF and Tompkins, MB}, year={2004}, month={Apr}, pages={307–322} }
 @article{bull_vahlenkamp_dow_collisson_winslow_phadke_tompkins_tompkins_2004, title={Spontaneous T cell apoptosis in feline immunodeficiency virus (FIV)-infected cats is inhibited by IL2 and anti-B7.1 antibodies}, volume={99}, ISSN={["1873-2534"]}, DOI={10.1016/j.vetimm.2004.01.010}, abstractNote={Lymph node (LN) T cells from feline immunodeficiency virus (FIV)-infected cats have an increased expression of B7 co-stimulatory molecules as well as their ligand CTLA4, resembling an activation phenotype shown to induce anergy and apoptosis in activated T cells. In addition, LN T cells from FIV-infected cats also show increased spontaneous apoptosis compared to uninfected animals. The apoptosis observed in these animals occurs primarily in T cells expressing B7 and CTLA4, suggesting a role for B7 and CTLA4 interactions in the induction of anergy/apoptosis. In order to investigate the role of B7 and CTLA4 interactions on T cell apoptosis in LN T cells from FIV-infected cats, we performed blocking experiments by measuring T cell apoptosis in LN T cell cultures treated with anti-feline B7.1, B7.2, and CTLA4 specific antibodies, as well as interleukin (IL)-2. The addition of IL2, the primary cytokine produced by B7/CD28 interactions, resulted in a significant decrease of T cell apoptosis in cultured LN cells as assessed by two-color flow cytometry and TUNEL assay. The addition of anti-B7.1 antibodies significantly inhibited T cell apoptosis in FIV-infected cats with low-level plasma viremia, while addition of anti-B7.2 and anti-CTLA4 antibodies had no affect. These results suggest a role of B7 signaling in the increased spontaneous apoptosis observed in LN T cells from FIV-infected animals.}, number={1-2}, journal={VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY}, author={Bull, ME and Vahlenkamp, TW and Dow, JL and Collisson, EW and Winslow, BJ and Phadke, AP and Tompkins, MB and Tompkins, WAF}, year={2004}, month={May}, pages={25–37} }
 @article{feng_tompkins_xu_zhang_mccaw_2003, title={Analysis of constitutive cytokine expression by pigs infected in-utero with porcine reproductive and respiratory syndrome virus}, volume={94}, ISSN={["0165-2427"]}, DOI={10.1016/S0165-2427(03)00059-X}, abstractNote={To investigate cytokine alterations in pigs infected in-utero with porcine reproductive and respiratory syndrome virus (PRRSV), constitutive mRNA expression by peripheral blood mononuclear cells (PBMCs) was measured. PBMC from in-utero PRRSV-infected pigs displayed significantly increased IL-6, IL-10, and IFN-γ mRNA expression at 0 and 14 days of age compared with age-matched control pigs. There were no significant differences in IL-2, IL-4, and IL-12 mRNA expression between in-utero PRRSV-infected and control pigs. However, the IL-10/IL-12 ratio was significantly increased in in-utero PRRSV-infected pigs at 0 and 14 days of age, suggesting the imbalance of IL-10 and IL-12 mRNA production. The abnormal mRNA expression of cytokines in in-utero PRRSV-infected pigs occurred concurrently with a significant decrease in the CD4+/CD8+ T-cell ratio in peripheral blood. PRRSV was not isolated from the sera of pigs at 9 weeks of age that had been viremic at 0 and 14 days old. Delayed type hypersensitivity (DTH) responses to Tuberculin and analysis of cytokine mRNA expression by PBMC showed that cell-mediated immune response and cytokine message profiles in pigs infected in-utero with PRRSV had returned to levels similar to those of control pigs by 9 weeks of age. We conclude that in-utero infection with PRRSV results in significant alteration of cytokine mRNA expression that may cause transient immunomodulation. However, at 10 weeks of age the pigs’ immune responses seemed to recover. This may help to understand the immunopathogenesis of in-utero PRRSV infection and the increased susceptibility to secondary bacterial pathogens in neonatal piglets.}, number={1-2}, journal={VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY}, author={Feng, WH and Tompkins, MB and Xu, JS and Zhang, HX and McCaw, MB}, year={2003}, month={Jul}, pages={35–45} }
 @article{hudson_vahlenkamp_howard_colby_tompkins_meeker_2002, title={Cerebrospinal fluid centesis at the cerebellomedullary cistern of kittens}, volume={41}, number={5}, journal={Contemporary Topics in Laboratory Animal Science}, author={Hudson, L. C. and Vahlenkamp, T. W. and Howard, K. E. and Colby, B. and Tompkins, M. B. and Meeker, R. B.}, year={2002}, pages={30–32} }
 @article{bragg_hudson_liang_tompkins_fernandes_meeker_2002, title={Choroid plexus macrophages proliferate and release toxic factors in response to feline immunodeficiency virus}, volume={8}, ISSN={["1355-0284"]}, DOI={10.1080/13550280290049679}, abstractNote={Recent observations have suggested that lentiviruses stimulate the proliferation and activation of microglia. A similar effect within the dense macrophage population of the choroid plexus could have significant implications for trafficking of virus and inflammatory cells into the brain. To explore this possibility, we cultured fetal feline macrophages and examined their response to feline immunodeficiency virus (FIV) or the T-cell-derived protein, recombinant human CD40-ligand trimer (rhuCD40-L). The rhCD40-L was the most potent stimulus for macrophage proliferation, often inducing a dramatic increase in macrophage density. Exposure to FIV resulted in a small increase in the number of macrophages and macrophage nuclei labeled with bromodeoxyuridine. The increase in macrophage density after FIV infection also correlated with an increase in neurotoxic activity of the macrophage-conditione d medium. Starting at 16–18 weeks postinfection, well after the peak of viremia, a similar toxic activity was detected in cerebrospinal fluid (CSF) from FIV-infected cats. Toxicity in the CSF increased over time and was paralleled by strong CD18 staining of macrophages/microglia in the choroid plexus and adjacent parenchyma. These results suggest that lentiviral infection of the choroid plexus can induce a toxic inflammatory response that is fueled by local macrophage proliferation. Together with the observation of increasing toxic activity in the CSF and increased CD18 staining in vivo, these observations suggest that choroid plexus macrophages may contribute to an inflammatory cascade in the brain that progresses independently of systemic and CSF viral load.}, number={3}, journal={JOURNAL OF NEUROVIROLOGY}, author={Bragg, DC and Hudson, LC and Liang, YH and Tompkins, MB and Fernandes, A and Meeker, RB}, year={2002}, month={Jun}, pages={225–239} }
 @article{tompkins_bull_dow_ball_collisson_winslow_phadke_vahlenkamp_tompkins_2002, title={Feline immunodeficiency virus infection is characterized by B7(+)CTLA4(+) T cell apoptosis}, volume={185}, ISSN={["0022-1899"]}, DOI={10.1086/339847}, abstractNote={The B7.1 and B7.2 costimulatory molecules on antigen-presenting cells provide second signals for regulating T cell immune responses via CD28 and cytotoxic T lymphocyte antigen 4 (CTLA4) on T cells. CD28 signals cell proliferation, whereas CTLA4 signals for anergy or apoptosis, terminating the immune response. Because T cell apoptosis and immunodeficiency is a characteristic of feline immunodeficiency virus (FIV)-infected cats, it is possible that negative T cell signaling via B7 and CTLA4 may be favored in these cats. Flow cytometry revealed high percentages of CD8+ and CD4+ cells expressing B7.1, B7.2, and CTLA4 in lymph nodes of FIV-positive cats and a large fraction of CTLA4+ T cells coexpressing B7.1 and B7.2. Three-color analysis with anti-B7.1, anti-B7.2, or anti-CTLA4 and TUNEL (terminal deoxynucleotidyl transferase nick-end-labeling) analysis revealed that apoptosis was a characteristic of B7.1+ B7.2+ CTLA4+ T cells. These data support the hypothesis that lymph node apoptosis and immune deterioration in FIV-infected cats results from chronic B7.1- and/or B7.2-CTLA4-mediated T-T interactions.}, number={8}, journal={JOURNAL OF INFECTIOUS DISEASES}, author={Tompkins, MB and Bull, ME and Dow, JL and Ball, JM and Collisson, EW and Winslow, BJ and Phadke, AP and Vahlenkamp, TW and Tompkins, WA}, year={2002}, month={Apr}, pages={1077–1093} }
 @article{bragg_childers_tompkins_tompkins_meeker_2002, title={Infection of the choroid plexus by feline immunodeficiency virus}, volume={8}, ISSN={["1355-0284"]}, DOI={10.1080/13550280290049688}, abstractNote={The human, simian, and feline immunodeficiency viruses rapidly penetrate into the brain and trigger an inflammatory process that can lead to significant neurologic disease. However, the mechanisms that permit efficient trafficking of macrophage-tropic and the more neurotoxic lymphocytotropic isolates are still poorly understood. One potential source of virus entry may be the blood-CSF barrier provided by the choroid plexus. Infected cells are often detected within the choroid plexus but it is unclear whether this reflects trafficking cells or infection of the large macrophage population within the choroidal stroma. To address this issue, we cultured fetal feline choroid plexus and evaluated the ability of feline immunodeficiency virus (FIV) to establish a primary infection. Significant provirus was detected in macrophage-enriche d choroid plexus cultures as well as in the choroid plexus of cats infected in vivo. FIV p24 antigen production in vitro was very low but detectable. Addition of a feline T-cell line to macrophages inoculated with FIV resulted in a dense clustering of the T cells over macrophages with dendritic cell-like morphologies and a robust productive infection. The direct infection of choroid plexus macrophages with FIV, the efficient transfer of the infection to T cells indicate that the choroid plexus can be a highly efficient site of viral infection and perhaps trafficking of both macrophage-tropic and T-cell-tropic viruses into the CNS.}, number={3}, journal={JOURNAL OF NEUROVIROLOGY}, author={Bragg, DC and Childers, TA and Tompkins, MB and Tompkins, WA and Meeker, RB}, year={2002}, month={Jun}, pages={211–224} }
 @article{feng_tompkins_xu_brown_laster_zhang_mccaw_2002, title={Thymocyte and peripheral blood T lymphocyte subpopulation changes in piglets following in utero infection with porcine reproductive and respiratory syndrome virus}, volume={302}, ISSN={["0042-6822"]}, DOI={10.1006/viro.2002.1650}, abstractNote={Piglets infected in utero with porcine reproductive and respiratory syndrome virus (PRRSV) are born severely immunocompromised. In this article we more closely examine the effects of in utero PRRSV infection on circulating and thymic T cell populations. Numbers of CD4+, CD8+, and dual-positive lymphocytes were quantitated in circulation and in the thymus during the 2 weeks following birth. At birth we found that the number of circulating lymphocytes was suppressed by 60%. Lymphocyte numbers were also suppressed by 42% at day 7, but by day 14 the number of lymphocytes had rebounded and was actually 47% greater than controls. At birth and day 7, a drop in the number of CD4+ cells could partially explain the suppression we observed, while the rebound in total lymphocyte numbers seen at day 14 was due to a nearly fourfold increase in the number of circulating CD8+ cells. As a result, the normal CD4+:CD8+ ratio of between 1.4 and 2.2 for neonatal pigs was reduced to 0.1-0.5. The thymuses of infected piglets were found to be 50% smaller than those of control pigs and were characterized by cortical involution and severe cortical depletion of thymocytes. Analysis of the population of thymocytes revealed that double-positive thymocytes were suppressed to a greater degree than either single positive subpopulation. In addition, we show that the number of thymocytes undergoing apoptosis was increased twofold in piglets infected with PRRSV. Taken together, these results help explain the dramatic immunosuppression observed in neonatal animals infected in utero with PRRSV.}, number={2}, journal={VIROLOGY}, author={Feng, WH and Tompkins, MB and Xu, JS and Brown, TT and Laster, SM and Zhang, HX and McCaw, MB}, year={2002}, month={Oct}, pages={363–372} }
 @inproceedings{vahlenkamp_bull_dow_anderson_tompkins_tompkins_2001, title={B7.1/B7.2 and CTLA4 expression on feline T cells in vitro correlates with apoptosis}, number={2001}, booktitle={Journal of Leukocyte Biology}, author={Vahlenkamp, T. W. and Bull, M. E. and Dow, J. and Anderson, J. and Tompkins, M. B. and Tompkins, W. A. F.}, year={2001}, pages={255} }
 @article{ritchey_levy_bliss_tompkins_tompkins_2001, title={Constitutive expression of types 1 and 2 cytokines by alveolar macrophages from feline immunodeficiency virus-infected cats}, volume={79}, ISSN={["0165-2427"]}, DOI={10.1016/S0165-2427(01)00250-1}, abstractNote={Evidence suggests that feline immunodeficiency virus (FIV), causes pulmonary immunodeficiency. The overall objective of this study was to explore FIV-induced alterations in cell counts and cytokine gene expression in the pulmonary compartment during the acute stage infection. Bronchoalveolar lavage (BAL) cells were collected from FIV-infected and control cats at 0, 4, 10, and 16 weeks post-FIV infection for phenotype and cytokine analysis. The major change in BAL cellular populations following FIV-infection was the development of a neutrophilia. Total BAL cell counts and relative numbers of alveolar macrophages (AM), eosinophils, and lymphocytes remained similar in both groups. The RT-qcPCR analyses of AM purified from BAL showed constitutive expression of TNFα, IL6 and IL10 mRNAs that peaked during the acute stage of infection then declined. The TNFα and IL6 bioactive protein secretion showed a similar response. In contrast, IFNγ expression increased progressively with time after infection and paralleled a progressive increase in FIV-gag mRNA in AM. The IL12 p40 expression also differed from the other cytokines in that there was a progressive decrease in the number of cats with AM IL12 expression following FIV infection. Infection of AM in vitro with FIV also caused an increase in TNFα and IL6 mRNA and bioactive protein suggesting that the increased cytokine response by AM following infection of cats with FIV is an intrinsic characteristic of FIV-infected AM. In summary, pulmonary immune changes seen in FIV-infected cats are similar to those seen in HIV-infected human patients.}, number={1-2}, journal={VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY}, author={Ritchey, JW and Levy, JK and Bliss, SK and Tompkins, WAF and Tompkins, MB}, year={2001}, month={May}, pages={83–100} }
 @article{butterworth_english_jordan_tompkins_2001, title={Distribution of immune cells in the female reproductive tract in uninfected and FIV infected cats}, volume={83}, ISSN={["0165-2427"]}, DOI={10.1016/S0165-2427(01)00371-3}, abstractNote={Cell-free and cell-associated FIV effectively cross the mucosa of the feline female reproductive tract. To identify possible cellular targets of FIV and to characterize changes in mucosal immunity after infection, we examined the types and numbers of immune cells residing in the reproductive tracts of control and intravaginally FIV-infected cats. Sections of the vestibule, vagina, cervix, uterus, and ovaries, were examined by immunohistochemistry for CD4+ and CD8+ T lymphocytes, CD22+ B lymphocytes, CD1a+ dendritic cells, and CD14+ macrophages. The reproductive tract of uninfected cats contained substantial numbers of CD8+ T lymphocytes, CD4+ T lymphocytes and macrophages, as well as moderate numbers of CD1a+ dendritic cells, and few B lymphocytes. The most prominent change between FIV- and FIV+ cats was a marked decrease in the concentration of CD4+ T lymphocytes resulting in inverted CD4+:CD8+ ratios throughout the reproductive tract of infected cats. There was also a trend towards increasing numbers of CD1a+ dendritic cells in the intravaginally-infected FIV+ cats, and decreasing numbers of macrophages and CD22+ B lymphocytes. This study indicates that similar to the peripheral immune system, FIV infection is associated with CD4+ cell loss and reduced CD4+:CD8+ ratios in the female reproductive mucosal tissue.}, number={1-2}, journal={VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY}, author={Butterworth, JL and English, RV and Jordan, HL and Tompkins, MB}, year={2001}, month={Nov}, pages={37–51} }
 @inproceedings{tompkins_bull_dow_tompkins_2001, title={Feline immunodeficiency virus (FIV) infection induces B7(+)CTLA4(+) T cell apoptosis: A model for T cell depletion and immunodeficiency}, number={2001}, booktitle={Journal of Leukocyte Biology}, author={Tompkins, M. B. and Bull, M. E. and Dow, J. L. and Tompkins, W. A. F.}, year={2001}, pages={254} }
 @article{levy_richards_edwards_elston_hartmann_rodan_thayer_tompkins_wolf_2001, title={Feline retrovirus testing and management}, volume={23}, number={7}, journal={Compendium on Continuing Education for the Practicing Veterinarian}, author={Levy, J. and Richards, J. and Edwards, D. and Elston, T. and Hartmann, K. and Rodan, I. and Thayer, V. and Tompkins, M. and Wolf, A.}, year={2001}, pages={652-} }
 @article{pappalardo_brown_tompkins_breitschwerdt_2001, title={Immunopathology of Bartonella vinsonii (berkhoffii) in experimentally infected dogs}, volume={83}, ISSN={["1873-2534"]}, DOI={10.1016/S0165-2427(01)00372-5}, abstractNote={Following natural infection with Bartonella, dogs and humans develop comparable disease manifestations including endocarditis, peliosis hepatis, and granulomatous disease. As the immunologic response to infection in these hosts has not been clearly established, data presented here was derived from the experimental infection of six specific pathogen free (SPF) beagles with a known pathogenic strain of Bartonella. Six dogs were inoculated intravenously with 10(9)cfu of B. vinsonii ssp. berkhoffii and six control dogs were injected intravenously with an equivalent volume of sterile saline. Despite production of substantial levels of specific antibody, blood culture and molecular analyses indicated that Bartonella established chronic infection in these dogs. Flow cytometric analysis of monocytes indicated impaired bacterial phagocytosis during chronic Bartonella infection. There was also a sustained decrease in the percentage of CD8+ lymphocytes in the peripheral blood. Moreover, modulation of adhesion molecule expression (downregulation of L-selectin, VLA-4, and LFA-1) on CD8+ lymphocytes suggested quantitative and qualitative impairment of this cell subset in Bartonella-infected dogs. When compared with control dogs, flow cytometric analysis of lymph node (LN) cells from B. vinsonii infected dogs revealed an expanded population of CD4+ T cells with an apparent naïve phenotype (CD45RA+/CD62L+/CD49D(dim)). However, fewer B cells from infected dogs expressed cell-surface MHC II, implicating impaired antigen presentation to helper T cells within LN. Taken together, results from this study indicate that B. vinsonii establishes chronic infection in dogs which may result in immune suppression characterized by defects in monocytic phagocytosis, an impaired subset of CD8+ T lymphocytes, and impaired antigen presentation within LN.}, number={3-4}, journal={VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY}, author={Pappalardo, BL and Brown, TT and Tompkins, M and Breitschwerdt, EB}, year={2001}, month={Dec}, pages={125–147} }
 @article{feng_laster_tompkins_brown_xu_altier_gomez_benfield_mccaw_2001, title={In utero infection by porcine reproductive and respiratory syndrome virus is sufficient to increase susceptibility of piglets to challenge by Streptococcus suis type II}, volume={75}, ISSN={["1098-5514"]}, DOI={10.1128/JVI.75.10.4889-4895.2001}, abstractNote={ABSTRACT}, number={10}, journal={JOURNAL OF VIROLOGY}, author={Feng, WH and Laster, SM and Tompkins, M and Brown, T and Xu, JS and Altier, C and Gomez, W and Benfield, D and McCaw, MB}, year={2001}, month={May}, pages={4889–4895} }
 @misc{tompkins_tompkins_yang_2001, title={Nucleic acids obtained from the envelope coding region of feline immunodeficiency virus molecular clone designated JSY3}, volume={6,331,616}, number={2001 Dec. 18}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={Tompkins, W. A. and Tompkins, M. and Yang, J.-S.}, year={2001} }
 @inproceedings{bull_vahlenkamp_tompkins_tompkins_2001, title={T cell apoptosis in FIV-infected cats is blocked by the addition of antibodies to B7.1 and B7.2}, number={2001}, booktitle={Journal of Leukocyte Biology}, author={Bull, M. E. and Vahlenkamp, T. W. and Tompkins, M. B. and Tompkins, W. A. F.}, year={2001}, pages={256} }
 @article{liang_hudson_levy_ritchey_tompkins_tompkins_2000, title={T cells overexpressing interferon-gamma and interleukin-10 are found in both the thymus and secondary lymphoid tissues of feline immunodeficiency virus-infected cats}, volume={181}, ISSN={["0022-1899"]}, DOI={10.1086/315226}, abstractNote={Similar to human immunodeficiency virus type 1, feline immunodeficiency virus (FIV) replicates in the thymus of infected animals, causing marked alteration in thymic lymphocyte subpopulations. The immune phenotype and cytokine patterns in the thymus and secondary lymphoid tissues of FIV-infected cats were investigated. FIV infection caused an acute-stage transient reduction in CD4CD8 double-positive thymocytes, a marked increase in CD8 single-positive thymocytes, and formation of thymic B cell lymphoid follicles. Interferon (IFN)-gamma and interleukin (IL)-10 mRNA were up-regulated in both the thymus and lymph nodes of FIV-infected cats. Analysis of purified CD4 and CD8 cells revealed that CD4 cells produced most of the IL-10, whereas IFN-gamma was produced by both subsets. Quantitative-competitive reverse-transcription polymerase chain reaction analysis revealed that thymocytes, especially CD4CD8 thymocytes, had much greater levels of gag mRNA than did lymph node T cells. Thus, overexpression of IFN-gamma and IL-10 is a feature of the thymus and secondary lymphoid tissues of FIV-infected cats.}, number={2}, journal={JOURNAL OF INFECTIOUS DISEASES}, author={Liang, YH and Hudson, LC and Levy, JK and Ritchey, JW and Tompkins, WAF and Tompkins, MB}, year={2000}, month={Feb}, pages={564–575} }
 @article{leutenegger_holznagel_hofmann-lehmann_aubert_tompkins_lutz_2000, title={Vaccination with feline immunodeficiency virus induces CD4 epitope masking by soluble factors}, volume={73}, ISSN={["0165-2427"]}, DOI={10.1016/S0165-2427(00)00147-1}, abstractNote={Soluble factors are important effector mechanisms to control for lentiviral replication. Vaccination of cats with recombinant outer surface proteins (SU) of the FIV envelope protein in combination with complete Freund adjuvant (CFA) and rabies nucleocapsid (NC) protein led to significantly reduced viral loads [Leutenegger, C.M., Hofmann-Lehmann, R., Holznagel, E., Cuisinier, A.M., Wolfensberger, C., Duquesne, V., Cronier, J., Allenspach, K., Aubert, A., Ossent, P. , Lutz, H., 1998. AIDS Res. Hum. Retroviruses, 14(3) 275-283]. Lymphocytes from vaccinated and non-vaccinated cats were stained with two monoclonal antibodies, Fel7 and CAT30A, directed against the feline CD4 antigen. Peripheral blood lymphocytes from cats vaccinated with the SU glycoprotein, CFA and rabies NC protein showed a significantly reduced number of cells after staining with CAT30A, while the number in Fel7 positive lymphocytes remained unchanged. This decreased CAT30A fluorescent staining could be reproduced in vitro by pre-incubating FIV-negative lymphocytes with immune sera from cats in which reduced CAT30A staining was detected. Neither experimental infection nor vaccination with the unglycosylated SU protein alone resulted in this epitope masking. Furthermore, this masking phenomenon was negatively correlated with a decreased susceptibility to activation-induced cell death (AICD). These findings will be discussed based on the current knowledge of CD8(+) T-cell antiviral factors and their involvement in lentiviral infection and/or replication.}, number={3-4}, journal={VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY}, author={Leutenegger, CM and Holznagel, E and Hofmann-Lehmann, R and Aubert, A and Tompkins, MB and Lutz, H}, year={2000}, month={Mar}, pages={343–352} }
 @article{meeker_azuma_bragg_english_tompkins_1999, title={Microglial proliferation in cortical neural cultures exposed to feline immunodeficiency virus}, volume={101}, ISSN={["0165-5728"]}, DOI={10.1016/S0165-5728(99)00126-5}, abstractNote={Microglia are thought to play an important role in neurodegenerative changes due to infection with human or animal immunodeficiency viruses. Using feline immunodeficiency virus and cat neural cultures, we observed a dramatic increase in the accumulation of microglia from a basal rate of 5-7% day(-1) to 25-126% day(-1). Both live virus and heat-inactivated virus induced proliferation. Negligible proliferation was seen in purified microglial cultures. Conditioned medium from astrocytes or mixed neural cultures treated with feline immunodeficiency virus stimulated the proliferation of purified microglia. Disease progression may be facilitated by early non-infectious interactions of lentiviruses with neural tissue that promote the activation and proliferation of microglia.}, number={1}, journal={JOURNAL OF NEUROIMMUNOLOGY}, author={Meeker, RB and Azuma, Y and Bragg, DC and English, RV and Tompkins, M}, year={1999}, month={Nov}, pages={15–26} }
 @article{bragg_meeker_duff_english_tompkins_1999, title={Neurotoxicity of FIV and FIV envelope protein in feline cortical cultures}, volume={816}, ISSN={["0006-8993"]}, DOI={10.1016/S0006-8993(98)01177-9}, abstractNote={The neurotoxic effects of the feline immunodeficiency virus (FIV) and FIV envelope proteins were measured in primary cultures of feline cortical neurons. Envelope protein from the FIV-PPR strain promoted neuronal swelling and death, whereas envelope protein from the FIV-34TF10 isolate produced intermediate or negligible toxicity. No effect was observed in control cultures treated with envelope protein from the Epstein–Barr virus. A concentration–effect curve showed that FIV-PPR protein produced maximal toxicity at 200 pM protein and decreased toxicity at higher concentrations, which is consistent with previous reports of the HIV-1 surface glycoprotein, gp120. These effects required the presence of low concentrations of glutamate. Using the natural host cells as targets, the effects of envelope protein and infectious virions were directly compared. All of the toxic activity could be attributed to non-infectious interactions between the viral envelope and target cells. Addition of 1 μM tetrodotoxin failed to block the effects of FIV-PPR in the presence of 20 μM glutamate. Toxicity would appear to involve two steps in which the envelope protein first sensitizes neurons through non-synaptic interactions (TTX insensitive) thereby setting the stage for enhanced synaptic activation via glutamate receptors (TTX sensitive).}, number={2}, journal={BRAIN RESEARCH}, author={Bragg, DC and Meeker, RB and Duff, BA and English, RV and Tompkins, MB}, year={1999}, month={Jan}, pages={431–437} }
 @article{gebhard_dow_childers_alvelo_tompkins_tompkins_1999, title={Progressive expansion of an L-selectin-negative CD8 cell with anti-feline immunodeficiency virus (FIV) suppressor function in the circulation of FIV-infected cats}, volume={180}, ISSN={["0022-1899"]}, DOI={10.1086/315089}, abstractNote={The acute stage of feline immunodeficiency virus (FIV) infection is characterized by the appearance of a major CD8 subpopulation with reduced expression of the CD8 beta chain (CD8alpha+betalo). CD8 antiviral activity was subsequently shown to be mediated by the CD8alpha+betalo phenotype, which is the dominant CD8 phenotype in long-term infected cats. Two- and three-color flow cytometric analysis demonstrated that the CD8alpha+betalo subset is L-selectin negative (CD62L-) and has increased expression of CD44, CD49d, and CD18, consistent with an activation phenotype. The CD8alpha+betaloCD62L- cells but not the CD8alpha+betahiCD62L+ cells demonstrated strong antiviral activity in the FIV acute-infection assay. The progressive expansion of the CD8alpha+betaloCD62L- effector subset cells in FIV-infected cats parallels that seen in human immunodeficiency virus (HIV)-infected patients, suggesting that failure in homeostatic mechanisms regulating lymphocyte activation or trafficking (or both) may be a consequence of both HIV and FIV infections.}, number={5}, journal={JOURNAL OF INFECTIOUS DISEASES}, author={Gebhard, DH and Dow, JL and Childers, TA and Alvelo, JI and Tompkins, MB and Tompkins, WAF}, year={1999}, month={Nov}, pages={1503–1513} }
 @article{olivry_dean_tompkins_dow_moore_1999, title={Toward a canine model of atopic dermatitis: amplification of cytokine-gene transcripts in the skin of atopic dogs}, volume={8}, ISSN={["0906-6705"]}, DOI={10.1111/j.1600-0625.1999.tb00372.x}, abstractNote={Abstract:  The objectives of the present study were to characterize and compare the repertoire of cytokine‐genes transcribed in skin homogenates obtained from normal dogs and dogs with atopic dermatitis (AD) using a reverse‐transcriptase polymerase chain reaction and canine‐specific cytokine‐gene primers. Whereas IL‐4 and IL‐5 cytokine‐gene transcripts were detected more commonly in atopic skin biopsy homogenates, IL‐2 mRNA was amplified more often from normal control specimens. IFN‐γ mRNA was detected in 5/29 atopic specimens, 4 of them obtained from the only dog with chronic skin lesions. One‐fourth of atopic samples exhibited clear type‐2 cytokine profiles; the remainder did not demonstrate polarized repertoires. Conversely, type‐1 cytokine profiles were characterized in one‐fourth of normal control specimens. The present study establishes, for the first time, the transcription of type‐2 cytokine‐genes in the skin of dogs with AD. Future experiments investigating the cellular origin and dynamics of allergic cytokine‐gene transcription are needed to confirm whether or not canine AD could be considered an immunological model for a human disease.}, number={3}, journal={EXPERIMENTAL DERMATOLOGY}, author={Olivry, T and Dean, GA and Tompkins, MB and Dow, JL and Moore, PF}, year={1999}, month={Jun}, pages={204–211} }
 @article{levy_ritchey_rottman_davidson_liang_jordan_tompkins_tompkins_1998, title={Elevated interleukin-10-to-interleukin-12 ratio in feline immunodeficiency virus-infected cats predicts loss of type 1 immunity to Toxoplasma gondii}, volume={178}, ISSN={["0022-1899"]}, DOI={10.1086/515632}, abstractNote={Similar to human immunodeficiency virus, feline immunodeficiency virus (FIV) induces immunodeficiency and enhanced susceptibility to secondary pathogens. To explore cytokine alterations in lentivirus immunodeficiency, constitutive mRNA expression was measured in lymph nodes of healthy and FIV-infected cats before and after challenge with Toxoplasma gondii. Cytokine mRNA expression was similar in control and FIV-infected cats during the first 10 weeks after infection. At 16 weeks, interferon (IFN)-gamma, tumor necrosis factor-alpha, and interleukin (IL)-10 mRNA were increased in FIV-infected cats. Challenge with T. gondii induced an increase in IL-2, IFN-gamma, and IL-12 in the lymph nodes of control cats, whereas IFN-gamma and IL-10 but not IL-2 or IL-12 increased in the lymph nodes of FIV-T. gondii coinfected cats. These results indicate that FIV immunodeficiency may derive from a failure to generate an IL-12-dependent type 1 response and that an elevated level of IL-10 mRNA expression is a predictor of lentivirus immunodeficiency.}, number={2}, journal={JOURNAL OF INFECTIOUS DISEASES}, author={Levy, JK and Ritchey, JW and Rottman, JB and Davidson, MG and Liang, YH and Jordan, HL and Tompkins, WA and Tompkins, MB}, year={1998}, month={Aug}, pages={503–511} }
 @article{jordan_howard_bucci_butterworth_english_kennedy-stoskopf_tompkins_tompkins_1998, title={Horizontal transmission of feline immunodeficiency virus with semen from seropositive cats}, volume={41}, DOI={10.1016/s0165-0378(98)00070-9}, abstractNote={The AIDS virus of cat species, feline immunodeficiency virus (FIV), has been used extensively as an animal model of HIV-1 infection. This felid lentivirus shares many molecular and biochemical traits with HIV-1 and causes similar immunologic and clinical perturbations, most notably CD4+ cell loss, impaired cell-mediated immunity and increased susceptibility to opportunistic pathogens. Previous reports have shown that FIV is transmitted horizontally by biting and vertically in utero and through nursing. Our objective was to determine whether FIV could be venereally transmitted in domestic cats. In the first experiment, susceptibility of the female reproductive tract to mucosal transmission of the FIV isolate, NCSU1, was demonstrated via intravaginal inoculation with infected cultured cells. We next identified virus in electroejaculates from asymptomatic, chronically FIV-NCSU1-infected, adult males. A fragment of FIV gag provirus DNA was detected by nested polymerase chain reaction (PCR) in nonfractionated seminal cells and in swim-up sperm preparations. Additionally, replication-competent virus was isolated from cell-free seminal plasma and seminal cells by co-cultivation with a feline CD4+ T-cell line. In the third study, queens were artificially inseminated via an intrauterine laparoscopic technique with electroejaculates from FIV-NCSU1-infected males. Of six inseminations carried out with fresh semen, three resulted in infection of queens. Lastly, immunohistochemical studies identified potential virus target cell populations in normal female reproductive tissues. In conclusion, these experiments indicate that FIV infection in domestic cats may provide a unique small animal model of sexual transmission of HIV-1.}, number={1-2}, journal={Journal of Reproductive Immunology}, author={Jordan, H. L. and Howard, J. G. and Bucci, J. G. and Butterworth, J. L. and English, R. and Kennedy-Stoskopf, S. and Tompkins, M. B. and Tompkins, W. A.}, year={1998}, pages={341–357} }
 @article{elder_dean_hoover_hoxie_malim_mathes_neil_north_sparger_tompkins_et al._1998, title={Lessons from the cat: Feline immunodeficiency virus as a tool to develop intervention strategies against human immunodeficiency virus type 1}, volume={14}, ISSN={["0889-2229"]}, DOI={10.1089/aid.1998.14.797}, abstractNote={AIDS Research and Human RetrovirusesVol. 14, No. 9 Workshop Summary: Lessons from the Cat: Feline Immunodeficiency Virus as a Tool to Develop Intervention Strategies against Human Immunodeficiency Virus Type 1JOHN H. ELDER, GREGG A. DEAN, EDWARD A. HOOVER, JAMES A. HOXIE, MICHAEL H. MALIM, LAWRENCE MATHES, JAMES C. NEIL, THOMAS W. NORTH, ELLEN SPARGER, MARY B. TOMPKINS, WAYNE A.F. TOMPKINS, JANET YAMAMOTO, NAOYA YUHKI, NEILS C. PEDERSEN, and ROGER H. MILLERJOHN H. ELDERSearch for more papers by this author, GREGG A. DEANSearch for more papers by this author, EDWARD A. HOOVERSearch for more papers by this author, JAMES A. HOXIESearch for more papers by this author, MICHAEL H. MALIMSearch for more papers by this author, LAWRENCE MATHESSearch for more papers by this author, JAMES C. NEILSearch for more papers by this author, THOMAS W. NORTHSearch for more papers by this author, ELLEN SPARGERSearch for more papers by this author, MARY B. TOMPKINSSearch for more papers by this author, WAYNE A.F. TOMPKINSSearch for more papers by this author, JANET YAMAMOTOSearch for more papers by this author, NAOYA YUHKISearch for more papers by this author, NEILS C. PEDERSENSearch for more papers by this author, and ROGER H. MILLERSearch for more papers by this authorPublished Online:15 Mar 2009https://doi.org/10.1089/aid.1998.14.797AboutSectionsPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetailsCited ByEqual contributions of feline immunodeficiency virus and coinfections to morbidity in African lionsInternational Journal for Parasitology: Parasites and Wildlife, Vol. 16Pathogenesis of oral FIV infection21 September 2017 | PLOS ONE, Vol. 12, No. 9Structural features of the C8 antiviral peptide in a membrane-mimicking environmentBiochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1838, No. 3Accessory Genes Confer a High Replication Rate to Virulent Feline Immunodeficiency VirusJournal of Virology, Vol. 87, No. 14In Vivo Assessment of Natural Killer Cell Responses during Chronic Feline Immunodeficiency Virus Infection31 May 2012 | PLoS ONE, Vol. 7, No. 5FIV diversity: FIVPle 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(FIV-Apetaluma and FIV-Cpgammar) in young adult specific pathogen free catsVeterinary Immunology and Immunopathology, Vol. 79, No. 1-2FELINE IMMUNODEFICIENCY VIRUSHuman Immunodeficiency Virus and AIDS: Insights from Animal LentivirusesJournal of Virology, Vol. 74, No. 16Alteration of Substrate and Inhibitor Specificity of Feline Immunodeficiency Virus ProteaseJournal of Virology, Vol. 74, No. 10Structural studies of FIV and HIV-1 proteases complexed with an efficient inhibitor of FIV proteaseProteins: Structure, Function, and Genetics, Vol. 38, No. 1Construction of Infectious Feline Foamy Virus Genomes: Cat Antisera Do Not Cross-Neutralize Feline Foamy Virus Chimera with Serotype-Specific Env SequencesVirology, Vol. 266, No. 1Neurophysiologic and Immunologic Abnormalities Associated With Feline Immunodeficiency Virus Molecular Clone FIV-PPR DNA InoculationJournal of Acquired Immune Deficiency Syndromes, Vol. 23, No. 1Neurophysiologic and Immunologic Abnormalities Associated With Feline Immunodeficiency Virus Molecular Clone FIV-PPR DNA InoculationJAIDS Journal of Acquired Immune Deficiency Syndromes, Vol. 23, No. 1Site-specific Incorporation of Nucleoside Analogs by HIV-1 Reverse Transcriptase and the Template Grip Mutant P157SJournal of Biological Chemistry, Vol. 275, No. 1AIDS vaccination studies using feline immunodeficiency virus as a model: immunisation with inactivated whole virus suppresses viraemia levels following intravaginal challenge with infected cells but not following intravenous challenge with cell-free virusVaccine, Vol. 18, No. 1-2Cyanovirin-N Binds to gp120 To Interfere with CD4-Dependent Human Immunodeficiency Virus Type 1 Virion Binding, Fusion, and Infectivity but Does Not Affect the CD4 Binding Site on gp120 or Soluble CD4-Induced Conformational Changes in gp120Journal of Virology, Vol. 73, No. 5 Volume 14Issue 9Jun 1998 To cite this article:JOHN H. ELDER, GREGG A. DEAN, EDWARD A. HOOVER, JAMES A. HOXIE, MICHAEL H. MALIM, LAWRENCE MATHES, JAMES C. NEIL, THOMAS W. NORTH, ELLEN SPARGER, MARY B. TOMPKINS, WAYNE A.F. TOMPKINS, JANET YAMAMOTO, NAOYA YUHKI, NEILS C. PEDERSEN, and ROGER H. MILLER.Workshop Summary: Lessons from the Cat: Feline Immunodeficiency Virus as a Tool to Develop Intervention Strategies against Human Immunodeficiency Virus Type 1.AIDS Research and Human Retroviruses.Jun 1998.797-801.http://doi.org/10.1089/aid.1998.14.797Published in Volume: 14 Issue 9: March 15, 2009PDF download}, number={9}, journal={AIDS RESEARCH AND HUMAN RETROVIRUSES}, author={Elder, JH and Dean, GA and Hoover, EA and Hoxie, JA and Malim, MH and Mathes, L and Neil, JC and North, TW and Sparger, E and Tompkins, MB and et al.}, year={1998}, month={Jun}, pages={797–801} }
 @article{bucci_english_jordan_childers_tompkins_tompkins_1998, title={Mucosally transmitted feline immunodeficiency virus induces a CD8(+) antiviral response that correlates with reduction of cell-associated virus}, volume={177}, ISSN={["0022-1899"]}, DOI={10.1086/513822}, abstractNote={Intravaginal inoculation of cats with feline immunodeficiency virus (FIV) results in acute systemic infection accompanied by a strong CD8+ immune response that inhibits viral replication. CD8+ anti-FIV activity, revealed by increased FIV replication in peripheral blood mononuclear cells (PBMC) depleted of CD8+ lymphocytes, was detected by 6 weeks after inoculation and correlated with reduced PBMC-associated virus at 12, 16, and 32 weeks after inoculation. Some cats with strong CD8+ anti-FIV activity during acute infection did not seroconvert and yielded no evidence of FIV infection at later times. These data suggest that CD8+ immunity may play a major role in eliminating virus during primary transmucosal FIV infection and may down-regulate viral replication during asymptomatic infection.}, number={1}, journal={JOURNAL OF INFECTIOUS DISEASES}, author={Bucci, JG and English, RV and Jordan, HL and Childers, TA and Tompkins, MB and Tompkins, WAF}, year={1998}, month={Jan}, pages={18–25} }
 @article{bucci_gebhard_childers_english_tompkins_tompkins_1998, title={The CD8(+) cell phenotype mediating antiviral activity in feline immunodeficiency virus-infected cats is characterized by reduced surface expression of the CD8 beta chain}, volume={178}, ISSN={["0022-1899"]}, DOI={10.1086/515699}, abstractNote={The acute stage of feline immunodeficiency virus (FIV) infection is characterized by a CD8+ anti-FIV response that parallels the appearance of a CD8+ subpopulation with reduced expression of the beta chain (CD8 alpha + beta lo). The relationship between the CD8 alpha + beta lo phenotype and CD8+ anti-FIV activity was examined. Flow cytometric analysis of peripheral blood mononuclear cells with anti-CD8 beta chain monoclonal antibody 117 revealed that the CD8 alpha + beta lo phenotype expanded throughout the asymptomatic infection, constituting 80%-90% of the CD8 beta + cells in long-term-infected cats. Purified CD8 alpha + beta hi and CD8 alpha + beta lo subpopulations were analyzed for anti-FIV activity in an acute infection assay. Anti-FIV activity resided principally in the CD8 alpha + beta lo population and was demonstrated in acute FIV infections, as well as in long-term asymptomatic infections. These data suggest that a unique CD8 alpha + beta lo anti-FIV phenotype arises early in infection and may play a major role in eliminating virus and maintaining the asymptomatic infection.}, number={4}, journal={JOURNAL OF INFECTIOUS DISEASES}, author={Bucci, JG and Gebhard, DH and Childers, TA and English, RV and Tompkins, MB and Tompkins, WAF}, year={1998}, month={Oct}, pages={968–977} }
 @article{meeker_thiede_hall_english_tompkins_1997, title={Cortical cell loss in asymptomatic cats experimentally infected with feline immunodeficiency virus}, volume={13}, ISSN={["0889-2229"]}, DOI={10.1089/aid.1997.13.1131}, abstractNote={Specific pathogen-free cats experimentally infected with feline immunodeficiency virus (FIV) were used to evaluate the development of central nervous system changes during the asymptomatic stages of viral infection. The brains of asyptomatic cats were examined at postinoculation times ranging from 8 weeks to 3 years for changes in neuron density, glutamate receptor density, and synaptophysin immunoreactivity. At 2-3 years postinoculation a small decrease in neuronal density was found in layers 2-3 and layer 5 of the frontal cortex (-14.4%), parietal cortex (-18.1%), and striatum (-29.5%). The only other indications of pathology within these regions were a mild diffuse astrogliosis, occasional microglial nodules, and the accumulation of satellite cells around selected neurons. An average loss of large neurons of 56-68% was seen in the cortex of four random source cats euthanized with AIDS. These values contrasted with the absence of any significant cell loss in FIV-infected cats 18 weeks after inoculation or FIV-negative controls. The loss of neurons in the asymptomatic cats showed a significant positive correlation with a decrease in the blood CD4:CD8 ratios. Morphometric evaluation of synaptic terminal densities immunocytochemically stained with synaptophysin revealed a significant increase in the asymptomatic cats at 2-3 years postinoculation that correlated negatively with the CD4:CD8 ratios. Random source AIDS cats showed a 34% decrease in synaptophysin-immunoreactive profiles. Glutamate binding in the cortex did not change significantly in the asymptomatic cats (4-7% decline). Thus, experimentally infected specific pathogen-free cats show a loss of cortical neurons similar to what has been observed in postmortem studies of humans infected with HIV. The detection of neuronal loss during the asymptomatic stage of disease and the correlation with the peripheral CD4:CD8 cell ratios indicate that neurodegeneration may progress in parallel with peripheral disease.}, number={13}, journal={AIDS RESEARCH AND HUMAN RETROVIRUSES}, author={Meeker, RB and Thiede, BA and Hall, C and English, R and Tompkins, M}, year={1997}, month={Sep}, pages={1131–1140} }
 @misc{tompkins_tompkins_1997, title={Feline immunodeficiency virus isolate NCSU.sub.1}, volume={5,665,592}, number={1997 Sept. 9}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={Tompkins, W. A. F. and Tompkins, M. B.}, year={1997} }
 @article{ruslander_gebhard_tompkins_grindem_page_1997, title={Immunophenotypic characterization of canine lymphoproliferative disorders}, volume={11}, number={2}, journal={In Vivo (Athens, Greece)}, author={Ruslander, D. A. and Gebhard, D. H. and Tompkins, M. B. and Grindem, C. B. and Page, R. L.}, year={1997}, pages={169–172} }
 @misc{tompkins_tompkins_1995, title={Feline immunodeficiency virus isolate NCSU.sub.1Lb}, volume={5413927}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={Tompkins, W. A. F. and Tompkins, M. B.}, year={1995} }
 @article{tompkins_1993, title={Diagnosis of feline retroviral infections}, volume={14}, number={4}, journal={Veterinary Technician}, author={Tompkins, M. B.}, year={1993}, pages={205} }
 @article{tompkins_nelson_english_novotney_1991, title={Early events in the immunopathogenesis of feline retrovirus infections}, volume={199}, number={10}, journal={Journal of the American Veterinary Medical Association}, author={Tompkins, M. B. and Nelson, P. D. and English, R. V. and Novotney, C.}, year={1991}, pages={1311} }
 @article{tompkins_gebhard_bingham_hamilton_davis_tompkins_1990, title={CHARACTERIZATION OF MONOCLONAL-ANTIBODIES TO FELINE LYMPHOCYTES-T AND THEIR USE IN THE ANALYSIS OF LYMPHOCYTE TISSUE DISTRIBUTION IN THE CAT}, volume={26}, ISSN={["0165-2427"]}, DOI={10.1016/0165-2427(90)90115-9}, abstractNote={We describe the development of three monoclonal antibodies to feline T lymphocytes. Antibody 1.572 stains 93% of feline thymocytes, 49% of lymph node, and 65% of spleen lymphocytes. Two-color analysis shows 1.572 does not stain Ig-bearing cells, and 1.572-positive lymphocytes plus Ig-positive lymphocytes make up approximately 90% of peripheral blood lymphocytes (PBL), suggesting that 1.572 is a pan-T cell marker. The other two monoclonal antibodies, 3.357 and CAT30A, stain a smaller population of thymocytes (59%) of which 40% express both antigens. The 3.357 antigen is found on 23% of lymph node and 47% of spleen lymphocytes, while the CAT30A antigen is found on 29% of lymph node and 19% of spleen lymphocytes. Two-color analysis shows that 3.357 and CAT30A stain mutually exclusive subpopulations of 1.572-positive cells. Using thymocytes as an antigen source, antibody 3.357 precipitated a molecule of 66,000 molecular weight (Mw) under nonreducing conditions and a heterodimer of 32,000 and 34,000 under reducing conditions, suggesting that 3.357 recognizes the feline CD8 homologue. Antibody CAT30A precipitated a molecule of 55,000 Mw under both reducing and nonreducing conditions, which suggests it recognizes the feline CD4 homologue. Analysis of PBL profiles of 35 normal cats using the three monoclonal antibodies indicates that the distribution of feline PBL subpopulations is similar to man, including the CAT30A:3.357 ratio (1.74), which is identical to reported CD4:CD8 ratios in man. Based on these data, the feline CD4 and CD8 homologues are similar to those reported in other species.}, number={4}, journal={VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY}, author={TOMPKINS, MB and GEBHARD, DH and BINGHAM, HR and HAMILTON, MJ and DAVIS, WC and TOMPKINS, WAF}, year={1990}, month={Dec}, pages={305–317} }
 @article{tompkins_novotney_grindem_page_english_nelson_tompkins_1990, title={HUMAN RECOMBINANT INTERLEUKIN-2 INDUCES MATURATION AND ACTIVATION SIGNALS FOR FELINE EOSINOPHILS INVIVO}, volume={48}, ISSN={["0741-5400"]}, DOI={10.1002/jlb.48.6.531}, abstractNote={Abstract}, number={6}, journal={JOURNAL OF LEUKOCYTE BIOLOGY}, author={TOMPKINS, MB and NOVOTNEY, C and GRINDEM, CB and PAGE, R and ENGLISH, R and NELSON, P and TOMPKINS, WAF}, year={1990}, month={Dec}, pages={531–540} }
 @article{tompkins_ogilvie_gast_franklin_weigel_tompkins_1989, title={Interleukin-2 suppression in cats naturally infected with feline leukemia virus}, volume={8}, number={1}, journal={Journal of Biological Response Modifiers}, author={Tompkins, M. B. and Ogilvie, G. K. and Gast, A. M. and Franklin, R. and Weigel, R. and Tompkins, W. A. F.}, year={1989}, pages={86} }