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 E Sarvetnick, Allan J. Tobin, Paul V. Lehmann, Daniel L. Kaufman

Research output: Contribution to journalArticle

230 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Inbred NOD Mouse
T-cells
Autoantigens
Graft Survival
Medical problems
Autoimmunity
Grafts
Disease Progression
T-Lymphocytes
Self Tolerance
Th1 Cells
Anti-Inflammatory Agents
Down-Regulation
Modulation
Transplants
To autoantigen
Therapeutics
glutamate decarboxylase 2

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., ... 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

Modulating autoimmune responses to GAD inhibits disease progression and prolongs islet graft survival in diabetes-prone mice. / Tian, Jide; Clare-Salzler, Michael; Herschenfeld, Alan; Middleton, Blake; Newman, Douglas; Mueller, Regula; Arita, Seiji; Evans, Christopher; Atkinson, Mark A.; Mullen, Yoko; Sarvetnick, Nora E; Tobin, Allan J.; Lehmann, Paul V.; Kaufman, Daniel L.

In: Nature Medicine, Vol. 2, No. 12, 01.12.1996, p. 1348-1353.

Research output: Contribution to journalArticle

Tian, J, Clare-Salzler, M, Herschenfeld, A, Middleton, B, Newman, D, Mueller, R, Arita, S, Evans, C, Atkinson, MA, Mullen, Y, Sarvetnick, NE, Tobin, AJ, Lehmann, PV & Kaufman, DL 1996, 'Modulating autoimmune responses to GAD inhibits disease progression and prolongs islet graft survival in diabetes-prone mice', Nature Medicine, vol. 2, no. 12, pp. 1348-1353. https://doi.org/10.1038/nm1296-1348
Tian, Jide ; Clare-Salzler, Michael ; Herschenfeld, Alan ; Middleton, Blake ; Newman, Douglas ; Mueller, Regula ; Arita, Seiji ; Evans, Christopher ; Atkinson, Mark A. ; Mullen, Yoko ; Sarvetnick, Nora E ; Tobin, Allan J. ; Lehmann, Paul V. ; Kaufman, Daniel L. / Modulating autoimmune responses to GAD inhibits disease progression and prolongs islet graft survival in diabetes-prone mice. In: Nature Medicine. 1996 ; Vol. 2, No. 12. pp. 1348-1353.
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