| First Author | Wagner DH Jr | Year | 2002 |
| Journal | Proc Natl Acad Sci U S A | Volume | 99 |
| Issue | 6 | Pages | 3782-7 |
| PubMed ID | 11891296 | Mgi Jnum | J:126524 |
| Mgi Id | MGI:3761459 | Doi | 10.1073/pnas.052247099 |
| Citation | Wagner DH Jr, et al. (2002) Expression of CD40 identifies a unique pathogenic T cell population in type 1 diabetes. Proc Natl Acad Sci U S A 99(6):3782-7 |
| abstractText | 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. |
