Expression of CD40 identifies a unique pathogenic T cell population in type 1 diabetes

摘要: Juvenile diabetes (type 1) is an autoimmune disease in which CD4(+) T cells play a major role pathogenesis characterized by insulitis and beta cell destruction leading to clinical hyperglycemia. To date, no marker for has been described, although it was previously demonstrated that mice have large population of express CD40. We show here established, diabetogenic clones either the Th1 or Th2 phenotype are CD40-positive, whereas nondiabetogenic CD40-negative. CD40 functionally signals clones, inducing rapid activation transcription factor NFkappaB. diabetes-prone nonobese diabetic high levels CD40(+)CD4(+) thymus, spleen, importantly, pancreas. Finally, as adoptive transfers, CD4(+)CD40(+) infiltrate pancreatic islets causing beta-cell degranulation ultimately diabetes.