Administering glutamic acid decarboxylase to NOD mice prevents diabetes.
Type 1 diabetes is the result of an ongoing autoimmune response to specific proteins expressed by the insulin producing beta cells. Recently, a number of beta cell autoantigens have been identified. However, their role in mediating the diabetogenic response is not known. Here we assess the relative importance of a panel of beta cell autoantigens in the disease process. The approach was to inhibit T cell proliferation to a given autoantigen by either i.t. or i.v. injections, and then determine the effect this had on the diabetogenic response. We show that administering murine glutamic acid decarboxylase (GAD) to 3-week-old NOD females can reduce the frequency of insulitis and prevent the onset of diabetes. In contrast, carboxypeptidase H or peripherin do not induce a similar protective effect, suggesting that GAD has a critical role in the diabetogenic response. These results also suggest that GAD may provide a useful target for antigen-specific immunotherapy.
Tisch
R
R
Department of Microbiology and Immunology, Stanford University Medical Center, CA 94305.
Yang
X D
XD
Liblau
R S
RS
McDevitt
H O
HO
D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000008:administration & dosage*; D003922:Diabetes Mellitus, Type 1 / Q000517:prevention & control*; D005260:Female; D005968:Glutamate Decarboxylase / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D016688:Mice, Inbred NOD; D013601:T-Lymphocytes / Q000276:immunology*
D001323:Autoantibodies; D001324:Autoantigens; D005968:Glutamate Decarboxylase