PMID: 15240665Jul 9, 2004Paper

Expression of the B7.1 costimulatory molecule on pancreatic beta cells abrogates the requirement for CD4 T cells in the development of type 1 diabetes

The Journal of Immunology : Official Journal of the American Association of Immunologists
Evis HavariMyra A Lipes

Abstract

Although HLA-DQ8 has been implicated as a key determinant of genetic susceptibility to human type 1 diabetes, spontaneous diabetes has been observed in HLA-DQ8 transgenic mice that lack expression of murine MHC class II molecules (mII(-/-)) only when the potent costimulatory molecule, B7.1, is transgenically expressed on pancreatic beta cells. To study the contribution of HLA-DQ8 to the development of diabetes in this model, we crossed RIP-B7.1mII(-/-) mice with a set of transgenic mouse lines that differed in their HLA-DQ8 expression patterns on APC subpopulations, in particular dendritic cells and cortical thymic epithelial cells. Surprisingly, we found that even in the absence of HLA-DQ8 and CD4 T cells, a substantial fraction of the RIP-B7.1mII(-/-) mice developed diabetes. This disease process was remarkable for not only showing insulitis, but also inflammatory destruction of the exocrine pancreas with diffusely up-regulated expression of MHC class I and ICAM-1 molecules. Expression of HLA-DQ8 markedly increased the kinetics and frequency of diabetes, with the most severe disease in the lines with the highest levels of HLA-DQ8 on cortical thymic epithelial cells and the largest numbers of CD4 T cells. However, the adoptive...Continue Reading

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Citations

Jun 16, 2012·Science Translational Medicine·Raju V S R K GottumukkalaMyra A Lipes
Oct 8, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Aito UenoYang Yang
Jul 26, 2011·Clinical & Developmental Immunology·Roberto MalloneChristian Boitard
Aug 28, 2020·Drug Metabolism Reviews·Takeshi SusukidaKousei Ito
Mar 26, 2011·The Journal of Clinical Investigation·Huijuan LvMyra A Lipes

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