Induction of GAD65-Specific Regulatory T-Cells Inhibits Ongoing Autoimmune Diabetes in Nonobese Diabetic Mice

摘要

IDDM is a T-cell-mediated autoimmune disease in which the insulin-producing β-cells are destroyed. The disease process is complex, involving the recognition of several β-cell autoantigens. One of these, GAD65, appears to have a critical and not fully defined role in IDDM in humans and in the NOD mouse. We provide evi- Dence that an ongoing diabetogenic response in NOD Mice can be suppressed after intravenous administra- Tion of GAD65, but not by other β-cell autoantigens. Furthermore, suppression of the diabetogenic response Is mediated by the induction of GAD65-specific CD4~+ Regulatory T-cells. Finally, cytokine analysis indicates That these CD4~+ regulatory T-cells have a T-helper 2 Phenotype.