SOCS-1 protects from virally-induced CD8 T cell mediated type 1 diabetes

Abstract

CD8+ cytotoxic T lymphocytes (CTL) can rapidly kill β-cells and therefore contribute to the development of type 1 diabetes (T1D). CTL-mediated β-cell killing can occur via perforin-mediated lysis, Fas-Fas-L interaction, and the secretion of TNF-α or IFN-γ. The secretion of IFN-γ can contribute to β-cell death directly by eliciting nitric oxide production, and indirectly by upregulating MHC class I and 'unmasking' β-cells for recognition by CTL. Earlier studies in the RIP-LCMV mouse model of diabetes showed that disruption of β-cell IFN-γ signaling alone abolished the direct detrimental effects of IFN-γ, but not MHC class I upregulation. Suppressor of cytokine signaling-1 (SOCS-1) represses s..