Expression of MHC class II antigens on islet cells in the pathogenesis of Type I diabetes

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This study has been performed to clarify the significance of major histocompatibiity complex (MHC) class II antigens on pancreatic beta-cells in the pathogenesis of Type 1 (insulin-dependent) diabetes mellitus.In non-obese diabetic (NOD) mice, an animal model for Type 1 diabetes, I-A antigen, one of mouse MHC class II antigens, was observed in islet cells of all NOD mice examined. Double staining with anti-insulin, glucagon, somatostatin or pancreatic polypeptide antibodies revealed that I-A positive cells corresponded with insulin cells.Following this observation, we examined the pancreas biopsy specimens from 7 newly diagnosed Type 1 diabetic patients. Several features were revealed including marked decrease of insuli-containing cells, preservation of glucagon-containing cells, and various degrees of expression of MHC class I and class II antigens in islet cells and endothelial cells within and around the islets. In one patient, MHC class II antigens were clearly detected in insulin-containing cells. Electron microscopical examination showed the presence of a few lymphocytes infiltrating some islets of another patient.These results suggest that islet cells are destructed through immunological mechanisms and MHC class II antigens on insulin-containing cells may play an important role in the pathogenesis of Type 1 diabetes.