Expression of CD40 identifies a unique pathogenic T cell population in type 1 diabetes
Expression of CD40 identifies a unique pathogenic T cell population in type 1 diabetes
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DOI：
10.1073/pnas.052247099
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发表时间：
2002-03-19
影响因子：
11.1
通讯作者：
Haskins, K
中科院分区：
文献类型：
--
作者：
Wagner, DH;Vaitaitis, G;Haskins, K
Juvenile diabetes (type 1) is an autoimmune disease in which CD4(+) T cells play a major role in pathogenesis characterized by insulitis and beta cell destruction leading to clinical hyperglycemia. To date, no marker for autoimmune T cells has been described, although it was previously demonstrated that autoimmune mice have a large population of CD4(+) cells that express CD40. We show here that established, diabetogenic T cell clones of either the Th1 or Th2 phenotype are CD40-positive, whereas nondiabetogenic clones are CD40-negative. CD40 functionally signals T cell clones, inducing rapid activation of the transcription factor NFkappaB. We show that autoimmune diabetes-prone nonobese diabetic mice have high levels of CD40(+)CD4(+) T cells in the thymus, spleen, and importantly, in the pancreas. Finally, as demonstrated by adoptive transfers, CD4(+)CD40(+) cells infiltrate the pancreatic islets causing beta-cell degranulation and ultimately diabetes.
