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Journal home Advance online publication Current issue Archive Press releases Focuses Guide to authors Online submission For referees Free online issue Contact the journal Subscribe Advertising work@npg Reprints and permissions About this site For librarians   NPG Resources Nature Nature Reviews Immunology Nature Medicine Nature Cell Biology NI Tutorial: Finding regulatory DNA regions Signaling Gateway Immunology & Cell Biology Mucosal Immunology Nature Conferences NPG Subject areas Biotechnology Cancer Chemistry Clinical Medicine Dentistry Development Drug Discovery Earth Sciences Evolution & Ecology Genetics Immunology Materials Science Medical Research Microbiology Molecular Cell Biology Neuroscience Pharmacology Physics Browse all publications Article Nature Immunology  4, 1102 - 1110 (2003) Published online: 12 October 2003; | doi:10.1038/ni988 Interaction of Tim-3 and Tim-3 ligand regulates T helper type 1 responses and induction of peripheral tolerance Catherine A Sabatos1, Sumone Chakravarti1, Eugene Cha1, Anna Schubart1, Alberto Sánchez-Fueyo2, Xin Xiao Zheng2, Anthony J Coyle3, Terry B Strom2, Gordon J Freeman4 & Vijay K Kuchroo1 1  Department of Neurology, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. 2  Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA. 3  Inflammation Department, Experimental Medicine Division, Millennium Pharmaceuticals, Cambridge, Massachusetts 02139, USA. 4  Department of Medical Oncology, Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA. Correspondence should be addressed to Vijay K Kuchroo vkuchroo@rics.bwh.harvard.eduT helper type 1 (TH1) immune responses are central in cell-mediated immunity, and a TH1-specific cell surface molecule called Tim-3 (T cell immunoglobulin domain, mucin domain) has been identified. Here we report the identification of a secreted form of Tim-3 that contains only the immunoglobulin (Ig) variable (V) domain of the full-length molecule. Fusion proteins (Tim-3−Ig) of both Tim-3 isoforms specifically bound CD4+ T cells, indicating that a Tim-3 ligand is expressed on CD4+ T cells. Administration of Tim-3−Ig to immunized mice caused hyperproliferation of TH1 cells and TH1 cytokine release. Tim-3−Ig also abrogated tolerance induction in TH1 cells, and Tim-3-deficient mice were refractory to the induction of high-dose tolerance. These data indicate that interaction of Tim-3 with Tim-3 ligand may serve to inhibit effector TH1 cells during a normal immune response and may be crucial for the induction of peripheral tolerance. MORE ARTICLES LIKE THIS These links to content published by NPG are automatically generated REVIEWS The TIM gene family: emerging roles in immunity and disease Nature Reviews Immunology Review (01 Jun 2003) NEWS AND VIEWS I-Tim-izing the pathways of counter-regulation Nature Immunology News and Views (01 Nov 2003) RESEARCH Tim-3 inhibits T helper type 1–mediated auto- and alloimmune responses and promotes immunological tolerance Nature Immunology Article (01 Nov 2003) Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease Nature Letters to Editor (31 Jan 2002) Class IV semaphorin Sema4A enhances T-cell activation and interacts with Tim-2 Nature Letters to Editor (10 Oct 2002)  See all 11 matches for Research  Top Abstract Previous | Next Table of contents Full text Download PDF Send to a friend Save this link Open Innovation Challenges Single-cell Analysis Platform Deadline: Dec 02 2009 Reward: $5,000 USD This Challenge is looking for novel approaches to analyzing changes at a single-cell level. This is... Novel Approaches to Protecting Maize from Insect Damage Deadline: Jan 31 2010 Reward: $20,000 USD The Seeker is looking for novel approaches to protecting maize from insect damage. This Challenge re... More Challenges Powered by: nature jobs Assistant or Associate Professor of Neurobiology Medical College of Georgia Augusta, GA United States Group Leader Positions IMP Vienna Austria More science jobs Post a job for free Competing financial interests Figures & Tables Supplementary info See also: News and Views by Wills-Karp et al. See also: Article by Sánchez-Fueyo et al. Export citation Search buyers guide:   ADVERTISEMENT

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