Modulating autoimmune responses to GAD inhibits disease progression and prolongs islet graft survival in diabetes-prone mice - PubMed (original) (raw)

. 1996 Dec;2(12):1348-53.

doi: 10.1038/nm1296-1348.

M Clare-Salzler, A Herschenfeld, B Middleton, D Newman, R Mueller, S Arita, C Evans, M A Atkinson, Y Mullen, N Sarvetnick, A J Tobin, P V Lehmann, D L Kaufman

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Modulating autoimmune responses to GAD inhibits disease progression and prolongs islet graft survival in diabetes-prone mice

J Tian et al. Nat Med. 1996 Dec.

Abstract

In nonobese diabetic (NOD) mice, beta-cell reactive T-helper type 1 (Th1) responses develop spontaneously and gradually spread, creating a cascade of responses that ultimately destroys the beta-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 beta-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.

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