@article{adams_collins_williams_holmes_hess_atkins_scheidemantle_liu_lodge_johnson_et al._2024, title={Myeloid cell MHC I expression drives CD8<SUP>+</SUP> T cell activation in nonalcoholic steatohepatitis}, volume={14}, ISSN={["1664-3224"]}, url={https://doi.org/10.3389/fimmu.2023.1302006}, DOI={10.3389/fimmu.2023.1302006}, abstractNote={Background & aims Activated CD8+ T cells are elevated in Nonalcoholic steatohepatitis (NASH) and are important for driving fibrosis and inflammation. Despite this, mechanisms of CD8+ T cell activation in NASH are largely limited. Specific CD8+ T cell subsets may become activated through metabolic signals or cytokines. However, studies in NASH have not evaluated the impact of antigen presentation or the involvement of specific antigens. Therefore, we determined if activated CD8+ T cells are dependent on MHC class I expression in NASH to regulate fibrosis and inflammation. Methods We used H2Kb and H2Db deficient (MHC I KO), Kb transgenic mice, and myeloid cell Kb deficient mice (LysM Kb KO) to investigate how MHC class I impacts CD8+ T cell function and NASH. Flow cytometry, gene expression, and histology were used to examine hepatic inflammation and fibrosis. The hepatic class I immunopeptidome was evaluated by mass spectrometry. Results In NASH, MHC class I isoform H2Kb was upregulated in myeloid cells. MHC I KO demonstrated protective effects against NASH-induced inflammation and fibrosis. Kb mice exhibited increased fibrosis in the absence of H2Db while LysM Kb KO mice showed protection against fibrosis but not inflammation. H2Kb restricted peptides identified a unique NASH peptide Ncf2 capable of CD8+ T cell activation in vitro. The Ncf2 peptide was not detected during fibrosis resolution. Conclusion These results suggest that activated hepatic CD8+ T cells are dependent on myeloid cell MHC class I expression in diet induced NASH to promote inflammation and fibrosis. Additionally, our studies suggest a role of NADPH oxidase in the production of Ncf2 peptide generation.}, journal={FRONTIERS IN IMMUNOLOGY}, author={Adams, Victoria R. and Collins, Leonard B. and Williams, Taufika Islam and Holmes, Jennifer and Hess, Paul and Atkins, Hannah M. and Scheidemantle, Grace and Liu, Xiaojing and Lodge, Mareca and Johnson, Aaron J. and et al.}, editor={Williams, Taufika Islam and Collins, Leonard B. and Kennedy, ArionEditors}, year={2024}, month={Jan} }
 @article{herrmann_mamo_holmes_mohammed_murphy_bizikova_2022, title={Long-term effects of ciclosporin and oclacitinib on mediators of tolerance, regulatory T-cells, IL-10 and TGF-beta, in dogs with atopic dermatitis}, ISSN={["1365-3164"]}, DOI={10.1111/vde.13140}, abstractNote={BACKGROUND
Atopic dogs often are managed with allergen-specific immunotherapy (AIT) and concurrent dosages of ciclosporin (CSA) or oclacitinib to alleviate their clinical signs. Both drugs might affect proper tolerance induction by inhibiting regulatory T-cell (Treg) induction.


HYPOTHESIS/OBJECTIVES
We evaluated Treg cell numbers and serum interleukin (IL)-10 and transforming growth factor-beta (TGF-β)1 levels in dogs diagnosed with atopic dermatitis (AD) and successfully treated with either CSA or oclacitinib for nine or more months.


ANIMALS
We included 15 dogs receiving oclacitinib, 14 dogs treated with CSA, 15 healthy dogs, 13 dogs with untreated moderate-to-severe AD and 15 atopic dogs controlled with AIT.


MATERIALS AND METHODS
Peripheral blood CD4+CD25+FOXP3+ T-cell percentages were determined using flow cytometry. Serum concentrations of IL-10 and TGF-β1 were measured by enzyme-linked immunosorbent assay.


RESULTS
The percentage of Treg cells in the CSA group was significantly lower in comparison with the healthy group (p = 0.0003), the nontreated AD group (p = 0.0056) or the AIT group (p = 0.0186). There was no significant difference in Treg cell percentages between the CSA and oclacitinib groups, nor between the oclacitinib and the healthy, nontreated AD or AIT-treated dogs. No significant differences were detected in IL-10 and TGF-β1 serum concentrations between the five groups.


CONCLUSIONS AND CLINICAL RELEVANCE
Lower Treg cell percentages in the CSA-treated dogs suggest an impact of this drug on this cell population; however, it does not necessarily mean that it diminishes tolerance. Functionality and cytokine production may be more important than the number of Treg cells. Further studies evaluating the treatment outcome of dogs receiving AIT and concurrent drugs are needed to show clinical relevance.}, journal={VETERINARY DERMATOLOGY}, author={Herrmann, Ina and Mamo, Lisa B. and Holmes, Jenny and Mohammed, Javid P. and Murphy, K. Marcia and Bizikova, Petra}, year={2022}, month={Dec} }
 @article{nemec_holmes_hess_2021, title={Dog leukocyte antigen-88*034:01 presents nonamer peptides from canine distemper virus hemagglutinin, large polymerase, and matrix proteins}, volume={97}, ISSN={["2059-2310"]}, url={https://doi.org/10.1111/tan.14197}, DOI={10.1111/tan.14197}, abstractNote={Canine spontaneous cancers may offer greater fidelity than rodent models in advancing clinical immunotherapies. Boxers in particular are distinguished as study subjects by their popularity, and high incidence of human‐relevant cancers. Further, the MHC class I allele DLA‐88*034:01, with a known motif, dominates the breed, facilitating discovery of shared CTL responses against mutation‐origin neoepitopes by standard prediction methods. We experimentally confirmed the allomorph's binding motif by developing an MHC surface stabilization assay. The assay validated four DLA‐88*034:01‐presented peptides from canine distemper virus, ubiquitously administered in routine vaccines, for positive controls in future CTL studies. In turn, these viral peptides substantiated motif‐based prediction for DLA‐88*034:01. The study adds new tools for studying neoepitope‐specific CTL in Boxers to foster canine comparative oncology.}, number={5}, journal={HLA}, publisher={Wiley}, author={Nemec, Paige S. and Holmes, Jennifer C. and Hess, Paul R.}, year={2021}, month={May}, pages={428–434} }
 @article{holmes_scholl_dickey_hess_2021, title={High-resolution characterization of the structural features and genetic variation of six feline leukocyte antigen class I loci via single molecule, real-time (SMRT) sequencing}, volume={6}, ISSN={["1432-1211"]}, DOI={10.1007/s00251-021-01221-w}, journal={IMMUNOGENETICS}, author={Holmes, Jennifer C. and Scholl, Elizabeth H. and Dickey, Allison N. and Hess, Paul R.}, year={2021}, month={Jun} }