INDUCTION OF GAD65-SPECIFIC REGULATORY T-CELLS INHIBITS ONGOING AUTOIMMUNE DIABETES IN NONOBESE DIABETIC MICE

IDDM is a T-cell-mediated autoimmune disease in which the insulin-prod ucing beta-cells are destroyed. The disease process is complex, involv ing the recognition of several beta-cell autoantigens. One of these, G AD65, appears to have a critical and not fully defined role in IDDM in humans and in the NOD mouse. We provide evidence that an ongoing diab etogenic response in NOD mice can be suppressed after intravenous admi nistration of GAD65, but not by other beta-cell autoantigens. Furtherm ore, suppression of the diabetogenic response is mediated by the induc tion of GAD65-specific CD4(+) regulatory T-cells. Finally cytokine ana lysis indicates that these CD4(+) regulatory T-cells have a T-helper 2 phenotype.