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Glutamic Acid Decarboxylase‐Specific CD4 + Regulatory T Cells
Author(s) -
LIU CHIHPIN
Publication year - 2006
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1375.025
Subject(s) - antigen , immune system , nod , glutamate decarboxylase , nod mice , biology , t cell , immunology , antigen presenting cell , type 1 diabetes , diabetes mellitus , autoimmunity , endocrinology , biochemistry , enzyme
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.