Journal article
Interferons limit autoantigen-specific CD8 T-cell expansion in the non-obese diabetic mouse
G Jhala, B Krishnamurthy, TC Brodnicki, T Ge, S Akazawa, C Selck, PM Trivedi, EG Pappas, L Mackin, N Principe, E Brémaud, DJ De George, L Boon, I Smyth, J Chee, TWH Kay, HE Thomas
Cell Reports | CELL PRESS | Published : 2022
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 signali..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
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 husband-ry. 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 re-ceives support from the Operational Infrastructure Support Scheme of the Government of Victoria.