Tim-3 inhibits T helper type 1–mediated auto-and alloimmune responses and promotes immunological tolerance

A Sánchez-Fueyo, J Tian, D Picarella, C Domenig… - Nature …, 2003 - nature.com
A Sánchez-Fueyo, J Tian, D Picarella, C Domenig, XX Zheng, CA Sabatos, N Manlongat…
Nature immunology, 2003nature.com
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 …
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.
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