| First Author | Krishnamurthy B | Year | 2008 |
| Journal | J Immunol | Volume | 180 |
| Issue | 7 | Pages | 4458-64 |
| PubMed ID | 18354167 | Mgi Jnum | J:132969 |
| Mgi Id | MGI:3777478 | Doi | 10.4049/jimmunol.180.7.4458 |
| Citation | Krishnamurthy B, et al. (2008) Autoimmunity to Both Proinsulin and IGRP Is Required for Diabetes in Nonobese Diabetic 8.3 TCR Transgenic Mice. J Immunol 180(7):4458-4464 |
| abstractText | T cells specific for proinsulin and islet-specific glucose-6-phosphatase catalytic subunit related protein (IGRP) induce diabetes in nonobese diabetic (NOD) mice. TCR transgenic mice with CD8(+) T cells specific for IGRP(206-214) (NOD8.3 mice) develop accelerated diabetes that requires CD4(+) T cell help. We previously showed that immune responses against proinsulin are necessary for IGRP(206-214)-specific CD8(+) T cells to expand. In this study, we show that diabetes development is dramatically reduced in NOD8.3 mice crossed to NOD mice tolerant to proinsulin (NOD-PI mice). This indicates that immunity to proinsulin is even required in the great majority of NOD8.3 mice that have a pre-existing repertoire of IGRP(206-214)-specific cells. However, protection from diabetes could be overcome by inducing islet inflammation either by a single dose of streptozotocin or anti-CD40 agonist Ab treatment. This suggests that islet inflammation can substitute for proinsulin-specific CD4(+) T cell help to activate IGRP(206-214)-specific T cells. |
