Determinant Spreading of  T Helper Cell 2 (Th2) Responses to Pancreatic Islet Autoantigens

Tian, Jide; Lehmann, Paul V.; Kaufman, Daniel L.

doi:10.1084/jem.186.12.2039

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Brief Definitive Report| December 15 1997

Determinant Spreading of T Helper Cell 2 (Th2) Responses to Pancreatic Islet Autoantigens

Jide Tian,

Jide Tian

From the *Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California 90095-1735; and the ‡Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106

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Paul V. Lehmann,

Paul V. Lehmann

From the *Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California 90095-1735; and the ‡Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106

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Daniel L. Kaufman

From the *Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California 90095-1735; and the ‡Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106

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Author and Article Information

Jide Tian

From the *Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California 90095-1735; and the ‡Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106

Paul V. Lehmann

From the *Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California 90095-1735; and the ‡Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106

Daniel L. Kaufman

From the *Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California 90095-1735; and the ‡Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106

Address correspondence to Dr. Daniel L. Kaufman, Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Rm 23-167 CHS, University of California, Los Angeles, Los Angeles, CA 90095-1735. Phone: 310-794-9664; FAX: 310-825-6267; E-mail: [email protected]

Received: July 25 1997

Revision Received: September 12 1997

Online ISSN: 1540-9538

Print ISSN: 0022-1007

1997

J Exp Med (1997) 186 (12): 2039–2043.

https://doi.org/10.1084/jem.186.12.2039

The nature (Th1 versus Th2) and dynamics of the autoimmune response during the development of insulin-dependent diabetes mellitus (IDDM) and after immunotherapy are unclear. Here, we show in nonobese diabetic (NOD) mice that the autoreactive T cell response starts and spreads as a pure Th1 type autoimmunity, suggesting that a spontaneous Th1 cascade underlies disease progression. Surprisingly, induction of antiinflammatory Th2 responses to a single β cell antigen (βCA) resulted in the spreading of Th2 cellular and humoral immunity to unrelated βCAs in an infectious manner and protection from IDDM. The data suggest that both Th1 and Th2 autoimmunity evolve in amplificatory cascades by generating site-specific, but not antigen-specific, positive feedback circuits. Determinant spreading of Th2 responses may be a fundamental mechanism underlying antigen-based immunotherapeutics, explaining observations of infectious tolerance and providing a new theoretical framework for therapeutic intervention.

1997

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