Infectious Th1 and Th2 autoimmunity in diabetes-prone mice. NLM AIDSLINE Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

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Infectious Th1 and Th2 autoimmunity in diabetes-prone mice.

Immunol Rev. 1998 Aug;164:119-27. Unique Identifier : AIDSLINE MED/99011862
Tian J; Olcott AP; Hanssen LR; Zekzer D; Middleton B; Kaufman DL; Department of Molecular and Medical Pharmacology, University of; California, Los Angeles 90095-1735, USA.

Abstract: In the non-obese diabetic (NOD) mouse, a Th1-biased autoimmune response arises spontaneously against glutamic acid decarboxylase, concurrent with the onset of insulitis. Subsequently, Th1-type autoreactivity spreads intra- and intermolecularly to other beta-cell autoantigens (beta CAAs), suggesting that a spontaneous Th1 cascade underlies disease progression. Induction of Th2 immunity to a single beta CAA results in the spreading of Th2-type T-cell and humoral responses to other beta CAAs in an infectious manner. Thus, both Th1 and Th2 autoimmunity can evolve in amplificatory cascades defined by site-specific, but not antigen-specific, positive feedback circuits. Despite the continued presence of Th1 autoimmunity, the induction of Th2 spreading is associated with active tolerance to beta CAAs and reduced disease incidence. With disease progression there is an attenuation of beta CAA-inducible Th2 spreading, presumably because of a reduced availability of uncommitted beta CAA-reactive precursor T cells. We discuss the implications of these findings for the rational design of antigen-based immunotherapeutics.
Keywords: JOURNAL ARTICLE REVIEW REVIEW, TUTORIAL Animal *Autoimmunity Diabetes Mellitus, Non-Insulin-Dependent/*IMMUNOLOGY/THERAPY Epitope Mapping Immune Tolerance Islets of Langerhans/IMMUNOLOGY Mice Mice, Inbred NOD Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Th1 Cells/*IMMUNOLOGY Th2 Cells/*IMMUNOLOGYKWDjournalarticlereviewreview,tutorialanimalKWDautoimmunitydiabetesmellitus,non-insulin-dependent/KWDimmunology/therapyepitopemappingimmunetoleranceisletsoflangerhans/immunologymicemice,inbrednodsupport,non-uKWDsKWDgov'tsupport,uKWDsKWDgov't,pKWDhKWDsKWDth1cells/KWDimmunologyth2cells/KWDimmunology
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Copyright © 1999 - National Library of Medicine. Reproduced under license with the National Library of Medicine, Bethesda, MD.

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