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

Jide Tian, Michael Clare-Salzler, Alan Herschenfeld, Blake Middleton, Douglas Newman, Regula Mueller, Seiji Arita, Christopher Evans, Mark A. Atkinson, Yoko Mullen, Nora Sarvetnick, Allan J. Tobin, Paul V. Lehmann, Daniel L. Kaufman

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232 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1348-1353
Number of pages6
JournalNature Medicine
Volume2
Issue number12
DOIs
StatePublished - Dec 1 1996

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Tian, J., Clare-Salzler, M., Herschenfeld, A., Middleton, B., Newman, D., Mueller, R., Arita, S., Evans, C., Atkinson, M. A., Mullen, Y., Sarvetnick, N., Tobin, A. J., Lehmann, P. V., & Kaufman, D. L. (1996). Modulating autoimmune responses to GAD inhibits disease progression and prolongs islet graft survival in diabetes-prone mice. Nature Medicine, 2(12), 1348-1353. https://doi.org/10.1038/nm1296-1348