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

Type 1 diabetes results from destruction of pancreatic beta cells by autoreactive T cells. Both CD4 super(+) and CD8 super(+) T cells have been shown to mediate beta-cell killing. While CD8 super(+) T cells can directly recognize MHC class I on beta cells, the interaction between CD4 super(+) 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 super(+) T cells with T-cell receptors that recognize beta-cell antigens. Acute infiltration of CD4 super(+) 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- gamma increased MHC class II gene expression, and blocking IFN- gamma signaling in beta cells inhibited MHC class II upregulation. IFN- gamma also increased HLA-DR expression in human islets. MHC class II super(+) beta cells stimulated the proliferation of beta-cell-specific CD4 super(+) T cells. Our study indicates that MHC class II molecules may play an important role in beta-cell interaction with CD4 super(+) T cells in the development of type 1 diabetes.