Interferons limit autoantigen-specific CD8+ T-cell expansion in the non-obese diabetic mouse

Interferon gamma (IFN gamma) is a proinflammatory cytokine implicated in autoimmune diseases. However, deficiency or neutralization of IFN gamma 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). IFN gamma 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.

Automated summary

IFN gamma regulates the expansion of antigen-specific CD8(+) T cells by controlling the expression of SOCS-1. Despite reduced inflammation in Ifngr-mutant mice, the expanded CD8(+) T cells may contribute to normal diabetes progression.