Mouse pancreatic beta cells express MHC class II and stimulate CD4+ T cells to proliferate

Type 1 diabetes results from destruction of pancreatic beta cells by autoreactive T cells. Both CD4+ and CD8+ T cells have been shown to mediate beta‐cell killing. While CD8+ T cells can directly recognize MHC class I on beta cells, the interaction between CD4+ T cells and beta cells remains unclear. Genetic association studies have strongly implicated HLA‐DQ alleles in human type 1 diabetes. Here we studied MHC class II expression on beta cells in nonobese diabetic mice that were induced to develop diabetes by diabetogenic CD4+ T cells with T‐cell receptors that recognize beta‐cell antigens. Acute infiltration of CD4+ T cells in islets occurred with rapid onset of diabetes. Beta cells from islets with immune infiltration expressed MHC class II mRNA and protein. Exposure of beta cells to IFN‐γ increased MHC class II gene expression, and blocking IFN‐γ signaling in beta cells inhibited MHC class II upregulation. IFN‐γ also increased HLA‐DR expression in human islets. MHC class II+ beta cells stimulated the proliferation of beta‐cell‐specific CD4+ T cells. Our study indicates that MHC class II molecules may play an important role in beta‐cell interaction with CD4+ T cells in the development of type 1 diabetes.