Glutamic acid decarboxylase-specific CD4+ regulatory T cells.
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 1 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; (c) 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 1 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.
Liu
Chih-Pin
CP
Beckman Research Institute, City of Hope, Division of Immunology, 1450 E. Duarte, Duarte CA 91010, USA. cliu@coh.org
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology* / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000517:prevention & control; D005968:Glutamate Decarboxylase / Q000276:immunology*; D051379:Mice; D020297:Mice, Congenic; D016688:Mice, Inbred NOD; D009569:Nitric Oxide / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000201:enzymology / Q000276:immunology
D009569:Nitric Oxide; D005968:Glutamate Decarboxylase