@article{f31eeff56ba342c18adf2f3cd2cf12d1,
title = "Interferons limit autoantigen-specific CD8+ T-cell expansion in the non-obese diabetic mouse",
abstract = "Interferon gamma (IFNγ) is a proinflammatory cytokine implicated in autoimmune diseases. However, deficiency or neutralization of IFNγ is ineffective in reducing disease. We characterize islet antigen-specific T cells in non-obese diabetic (NOD) mice lacking all three IFN receptor genes. Diabetes is minimally affected, but at 125 days of age, antigen-specific CD8+ T cells, quantified using major histocompatibility complex class I tetramers, are present in 10-fold greater numbers in Ifngr-mutant NOD mice. T cells from Ifngr-mutant mice have increased proliferative responses to interleukin-2 (IL-2). They also have reduced phosphorylated STAT1 and its target gene, suppressor of cytokine signaling 1 (SOCS-1). IFNγ controls the expansion of antigen-specific CD8+ T cells by mechanisms which include increased SOCS-1 expression that regulates IL-2 signaling. The expanded CD8+ T cells are likely to contribute to normal diabetes progression despite reduced inflammation in Ifngr-mutant mice.",
keywords = "autoimmune diabetes, CP: Immunology, interferons, interleukin-2, MHC tetramers, suppressor of cytokine singling 1",
author = "Gaurang Jhala and Balasubramanian Krishnamurthy and Brodnicki, {Thomas C.} and Tingting Ge and Satoru Akazawa and Claudia Selck and Trivedi, {Prerak M.} and Pappas, {Evan G.} and Leanne Mackin and Nicola Principe and Erwan Br{\'e}maud and {De George}, {David J.} and Louis Boon and Ian Smyth and Jonathan Chee and Kay, {Thomas W.H.} and Thomas, {Helen E.}",
note = "Funding Information: We thank H.S. Quah, E. Po-Fan Chu, S. Fynch, K.L. Graham, T. Catterall, C. Tan, C. Anthony, V. Moshovakis, V. Madafferi, H. Barlow, and A. Cornelisz (St Vincent's Institute) for technical support, genotyping, and animal husbandry. CRISPR-Cas9 gene editing in NOD mice was performed at the Australian Phenomics Facility by L. Hawkey, D. Truman, and I. Smyth (Monash University, Clayton, Australia). This work was funded by National Health and Medical Research Council of Australia Program grants (GNT1126237 and GNT1150425) and project grant (GNT1145507) and a fellowship from JDRF and the Manpei Suzuki Diabetes Foundation (S.A.). St Vincent's Institute receives support from the Operational Infrastructure Support Scheme of the Government of Victoria. G.J. T.G. S.A. C.S. P.M.T. E.G.P. L.M. E.B. N.P. and D.J.D.G. designed and conducted experiments and collected and analyzed data. B.K. T.C.B. J.C. T.W.H.K. and H.E.T. designed the study, analyzed data, and wrote the manuscript. L.B. and I.S. provided reagents and wrote the manuscript. The authors declare no competing interests. Funding Information: We thank H.S. Quah, E. Po-Fan Chu, S. Fynch, K.L. Graham, T. Catterall, C. Tan, C. Anthony, V. Moshovakis, V. Madafferi, H. Barlow, and A. Cornelisz (St Vincent{\textquoteright}s Institute) for technical support, genotyping, and animal husbandry. CRISPR-Cas9 gene editing in NOD mice was performed at the Australian Phenomics Facility by L. Hawkey, D. Truman, and I. Smyth (Monash University, Clayton, Australia). This work was funded by National Health and Medical Research Council of Australia Program grants ( GNT1126237 and GNT1150425 ) and project grant ( GNT1145507 ) and a fellowship from JDRF and the Manpei Suzuki Diabetes Foundation (S.A.). St Vincent{\textquoteright}s Institute receives support from the Operational Infrastructure Support Scheme of the Government of Victoria. Publisher Copyright: {\textcopyright} 2022 The Authors",
year = "2022",
month = apr,
day = "26",
doi = "10.1016/j.celrep.2022.110747",
language = "English",
volume = "39",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Elsevier",
number = "4",
}
