Autoimmunity to both proinsulin and IGRP is required for diabetes in nonobese diabetic 8.3 TCR transgenic mice
- Author(s)
- Krishnamurthy, B; Mariana, L; Gellert, SA; Colman, PG; Harrison, LC; Lew, AM; Santamaria, P; Thomas, HE; Kay, TWH;
- Details
- Publication Year 2008-04-01,Volume 180,Issue #7,Page 4458-4464
- Journal Title
- JOURNAL OF IMMUNOLOGY
- Publication Type
- Journal Article
- Abstract
- 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)-specfic 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.
- Publisher
- AMER ASSOC IMMUNOLOGISTS
- Keywords
- PANCREATIC BETA-CELLS; T-CELLS; DENDRITIC CELLS; NOD MICE; CLASS-I; ISLET ANTIGENS; SELF-ANTIGENS; INSULIN; TOLERANCE; VIRUS
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- Refer to copyright notice on published article.
Creation Date: 2008-04-01 12:00:00