| First Author | Zhao Y | Year | 2015 |
| Journal | Eur J Immunol | Volume | 45 |
| Issue | 9 | Pages | 2494-503 |
| PubMed ID | 25959978 | Mgi Jnum | J:232829 |
| Mgi Id | MGI:5780272 | Doi | 10.1002/eji.201445378 |
| Citation | Zhao Y, et al. (2015) Mouse pancreatic beta cells express MHC class II and stimulate CD4(+) T cells to proliferate. Eur J Immunol 45(9):2494-503 |
| abstractText | Type 1 diabetes results from destruction of pancreatic beta cells by autoreactive T cells. Both CD4(+) and CD8(+) T cells have been shown to mediate beta-cell killing. While CD8(+) T cells can directly recognize MHC class I on beta cells, the interaction between CD4(+) 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(+) T cells with T-cell receptors that recognize beta-cell antigens. Acute infiltration of CD4(+) 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(+) beta cells stimulated the proliferation of beta-cell-specific CD4(+) T cells. Our study indicates that MHC class II molecules may play an important role in beta-cell interaction with CD4(+) T cells in the development of type 1 diabetes. |
