Tim-3 inhibits T helper type 1–mediated auto- and alloimmune responses and promotes immunological tolerance
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- 12 October 2003
- journal article
- research article
- Published by Springer Nature in Nature Immunology
- Vol. 4 (11) , 1093-1101
- https://doi.org/10.1038/ni987
Abstract
Although T helper (TH) cell–mediated immunity is required to effectively eliminate pathogens, unrestrained TH activity also contributes to tissue injury in many inflammatory and autoimmune diseases. We report here that the TH type 1 (TH1)-specific Tim-3 (T cell immunoglobulin domain, mucin domain) protein functions to inhibit aggressive TH1-mediated auto- and alloimmune responses. Tim-3 pathway blockade accelerated diabetes in nonobese diabetic mice and prevented acquisition of transplantation tolerance induced by costimulation blockade. These effects were mediated, at least in part, by dampening of the antigen-specific immunosuppressive function of CD4+CD25+ regulatory T cell populations. Our data indicate that the Tim-3 pathway provides an important mechanism to down-regulate TH1-dependent immune responses and to facilitate the development of immunological tolerance.Keywords
This publication has 48 references indexed in Scilit:
- Regulatory T cells in transplantation toleranceNature Reviews Immunology, 2003
- Regulatory T Cells Selectively Express Toll-like Receptors and Are Activated by LipopolysaccharideThe Journal of Experimental Medicine, 2003
- Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune diseaseNature, 2002
- The role of CD154-CD40 versus CD28-B7 costimulatory pathways in regulating allogeneic Th1 and Th2 responses in vivoJournal of Clinical Investigation, 2000
- Control of Autoimmune Diabetes in NOD Mice by GAD Expression or Suppression in β CellsScience, 1999
- Following the fate of individual T cells throughout activation and clonal expansion. Signals from T cell receptor and CD28 differentially regulate the induction and duration of a proliferative response.Journal of Clinical Investigation, 1997
- Duration of TCR Stimulation Determines Costimulatory Requirement of T CellsImmunity, 1996
- IMMUNE REGULATION BY CD40 AND ITS LIGAND GP39Annual Review of Immunology, 1996
- Lymphokine Production by Human T Cells in Disease StatesAnnual Review of Immunology, 1994
- Thymus and autoimmunity: capacity of the normal thymus to produce pathogenic self-reactive T cells and conditions required for their induction of autoimmune disease.The Journal of Experimental Medicine, 1990