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Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease

Monney, Laurent, Sabatos, Catherine A., Gaglia, Jason L., Ryu, Akemi, Waldner, Hanspeter, Chernova, Tatyana, Manning, Stephen, Greenfield, Edward A., Coyle, Anthony J., Sobel, Raymond A., Freeman, Gordon J., Kuchroo, Vijay K.·2002·Nature

Abstract

Activation of naive CD4(+) T-helper cells results in the development of at least two distinct effector populations, Th1 and Th2 cells. Th1 cells produce cytokines (interferon (IFN)-gamma, interleukin (IL)-2, tumour-necrosis factor (TNF)-alpha and lymphotoxin) that are commonly associated with cell-mediated immune responses against intracellular pathogens, delayed-type hypersensitivity reactions, and induction of organ-specific autoimmune diseases. Th2 cells produce cytokines (IL-4, IL-10 and IL-13) that are crucial for control of extracellular helminthic infections and promote atopic and allergic diseases. Although much is known about the functions of these two subsets of T-helper cells, there are few known surface molecules that distinguish between them. We report here the identification and characterization of a transmembrane protein, Tim-3, which contains an immunoglobulin and a mucin-like domain and is expressed on differentiated Th1 cells. In vivo administration of antibody to Tim-3 enhances the clinical and pathological severity of experimental autoimmune encephalomyelitis (EAE), a Th1-dependent autoimmune disease, and increases the number and activation level of macrophages. Tim-3 may have an important role in the induction of autoimmune diseases by regulating macrophage activation and/or function.

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Crossref · 10.1038/415536a

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Citations

Cites

Research works printed but not linked: 23

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Metadata

Authors
Monney, L., Sabatos, C. A., Gaglia, J. L., Ryu, A., Waldner, H., Chernova, T., Manning, S., Greenfield, E. A., Coyle, A. J., Sobel, R. A., Freeman, G. J., & Kuchroo, V. K.
Venue
Nature
Published
2002-01
Volume
415
Issue
6871
Pages
536-541
ISSN
  • 0028-0836
  • 1476-4687
Cited by
1,472
References
1
Language
en

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