Glutamic acid decarboxylase-specific CD4+ regulatory T cells

被引:5
作者
Liu, Chih-Pin [1 ]
机构
[1] City Hope Natl Med Ctr, Beckman Res Inst, Div Immunol, Duarte, CA 91010 USA
来源
IMMUNOLOGY OF DIABETES IV: PROGRESS IN OUR UNDERSTANDING | 2006年 / 1079卷
关键词
glutamic acid decarboxylase (GAD65); NOD mice; NOR mice; diabetes; regulatory T cells; antigen-presenting cells; nitric oxide;
D O I
10.1196/annals.1375.025
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
It is known that CD4(+) regulatory T cells (Tr cells) play a central role in inducing immune tolerance in animals and humans. Compared to polyclonal Tr cells, autoantigen-specific Tr cells are more potent at blocking pathogenic immune responses. In order to better understand the role of Tr cells in controlling type I diabetes development and to help design effective antigen-specific cell-based therapeutic methods to treat the disease, it is necessary to: (a) determine the antigen specificity of Tr cells; (b) study how antigen-specific Tr cells behave in vivo; (e) investigate the interaction of Tr cells with pathogenic T cells (Tpath cells) and determine whether such interaction correlates with the progression or inhibition of diabetes; and (d) determine the cellular and molecular mechanisms underlying the regulation of diabetes by Tr cells. We have addressed these questions with a focus on the studies of glutamic acid decarboxylase (GAD) specific T cells. Previous studies have suggested that GAD-specific T cells play a key role in type I diabetes. Treatment of NOD mice with GAD or its peptides can prevent the progression toward overt disease. The preventive effect could be due to either the deletion of antigen-specific pathogenic T cells or the induction of potent antigen-specific Tr cells. Using antigen-specific I-Ag7 tetramers we have isolated several populations of GAD peptide-specific T cells from diabetes-prone NOD and diabetes-resistant NOR mice. Herein, we summarize our studies on the role of these GAD peptide-specific T cells in type 1 diabetes. We present evidence that supports the hypothesis that the repertoire of T cells specific for these GAD peptides is biased toward Tr cells that inhibit diabetes rather than toward pathogenic T cells that induce diabetes.
引用
收藏
页码:161 / 170
页数:10
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