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-producing beta-cells are destroyed. The disease process is complex, involving the recognition of several beta-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 evidence that an ongoing diabetogenic response in NOD mice can be suppressed after intravenous administration of GAD65, but not by other beta-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.
Tisch
R
R
Department of Microbiology and Immunology, Stanford University Medical Center, California, USA.
Liblau
R S
RS
Yang
X D
XD
Liblau
P
P
McDevitt
H O
HO
D019264:Adoptive Transfer; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis* / Q000097:blood; D001324:Autoantigens / Q000276:immunology* / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology; D005968:Glutamate Decarboxylase / Q000276:immunology* / Q000494:pharmacology; D006801:Humans; D007515:Islets of Langerhans / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D016688:Mice, Inbred NOD; D013601:T-Lymphocytes / Q000276:immunology*
D001323:Autoantibodies; D001324:Autoantigens; D005968:Glutamate Decarboxylase