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 Tcells in non-obese diabetic (NOD) mice lacking all three IFN receptor genes. Diabetes is minimally affected, but at 125days of age, antigen-specific CD8+ Tcells, quantified using major histocompatibility complex class I tetramers, are present in 10-fold greater numbers in Ifngr-mutant NOD mice. Tcells 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+ Tcells by mechanisms which include increased SOCS-1 expression that regulates IL-2 signaling. The expanded CD8+ Tcells are likely to contribute to normal diabetes progression despite reduced inflammation in Ifngr-mutant mice.
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