@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{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{bull_kennedy-stoskopf_levine_loomis_gebhard_tompkins_2003, title={Evaluation of T lymphocytes in captive African lions (Panthera leo) infected with feline immunodeficiency virus}, volume={64}, ISSN={["0002-9645"]}, DOI={10.2460/ajvr.2003.64.1293}, abstractNote={Abstract}, number={10}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Bull, ME and Kennedy-Stoskopf, S and Levine, JF and Loomis, M and Gebhard, DG and Tompkins, WAF}, year={2003}, month={Oct}, pages={1293–1300} } @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{bull_gebhard_tompkins_kennedy-stoskopf_2002, title={Polymorphic expression in the CD8 alpha chain surface receptor of African lions (Panthera leo)}, volume={84}, ISSN={["1873-2534"]}, DOI={10.1016/S0165-2427(01)00401-9}, abstractNote={Free-ranging African lion (Panthera leo) peripheral blood mononuclear cells (PBMC) were examined using flow cytometry and antibodies developed for use in the domestic cat to determine if phenotypic changes occurred in lion lymphocytes as a result of feline immunodeficiency virus (FIV) infection. The percentage of CD8 cells from lion peripheral blood was considerably lower than in the domestic cat. Lions with elevated levels of CD8+ cells were typically infected with FIV, similar to observations in the domestic cat. Antibodies against the alpha chain of the CD8 receptor (monoclonal antibody (mAb) 3.357) did not react consistently in all lions examined. Flow cytometric analysis determined that approximately 82 and 80% of the animals from Kruger and Hluhluwe-Umfolozi National Parks in South Africa reacted with the monoclonal antibody against the alpha chain of CD8 receptor, while only 17% of the lions in Etosha National Park in Namibia cross-reacted with the CD8alpha chain. There was no apparent correlation between FIV status and CD8alpha chain reactivity. The relative isolation of Etosha from the other two parks could explain the marked difference in CD8alpha chain expression and suggests that lions similar to other mammalian species demonstrate polymorphic expression of the CD8alpha chain (197).}, number={3-4}, journal={VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY}, author={Bull, ME and Gebhard, DG and Tompkins, WAF and Kennedy-Stoskopf, S}, year={2002}, month={Jan}, pages={181–189} } @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} } @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} } @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} }