Modulating autoimmune responses to GAD inhibits disease progression and prolongs islet graft survival in diabetes–prone mice
- 1 December 1996
- journal article
- Published by Springer Science and Business Media LLC in Nature Medicine
- Vol. 2 (12), 1348-1353
- https://doi.org/10.1038/nm1296-1348
Abstract
In nonobese diabetic (NOD) mice, β–cell reactive T–helper type 1 (Th1) responses develop spontaneously and gradually spread, creating a cascade of responses that ultimately destroys the β–cells. The diversity of the autoreactive T–cell repertoire creates a major obstacle to the development of therapeutics. We show that even in the presence of established Th1 responses, it is possible to induce autoantigen–specific anti–inflammatory Th2 responses. Immune deviation of T–cell responses to the β–cell autoantigen glutamate decarboxylase (GAD65), induced an active form of self–tolerance that was associated with an inhibition of disease progression in prediabetic mice and prolonged survival of syngeneic islet grafts in diabetic NOD mice. Thus, modulation of autoantigen–specific Th1/Th2 balances may provide a minimally invasive means of downregulating established pathogenic autoimmune responses.Keywords
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