CD4+CD25+ regulatory T cells control the progression from periinsulitis to destructive insulitis in murine autoimmune diabetes
- 作者：Patrick A. Ott ; Michael R. Anderson ; Magdalena Tary-Lehmann and Paul V. Lehmann
- 关键词：Rodent ; Diabetes ; T cells ; Tolerance ; T regulatory cells
- 刊名：Cellular Immunology
- 出版年：2005
- 期刊代码：279_00088749
- 类别：med
- 出版时间：2005
- 卷：235
- 期：1
- 页码：1-11
- 文件大小：752 K
摘要
Non-obese diabetic (NOD) mice develop spontaneous T-cell responses against pancreatic β-cells, leading to islet cell destruction and diabetes. Despite high genetic similarity, non-obese resistant (NOR) mice do not develop diabetes. We show here that spleen cells of both NOD and NOR mice respond to the islet cell antigen glutamic acid decarboxylase-65 in IFN-γ-ELISPOT assays. Moreover, NOR-T cells induce periinsulitis in NOD SCID recipient mice. Thus, a potentially pathogenic islet cell-specific T-cell response arises in NOR and NOD mice alike; the mechanism that prevents the autoimmune progression of self-reactive T cells in NOR mice presumably acts at the level of effector function. Consistent with this hypothesis, CD4+CD25+ cell-depleted spleen cells from NOR mice mediated islet cell destruction and overt diabetes in NOD SCID mice. Therefore, islet cell-specific effector cells in NOR mice appear to be under the control of CD4+CD25+ regulatory T cells, confirming the importance of regulatory cells in the control of autoimmune diabetes.