Tim-3 inhibits T helper type 1–mediated auto- and alloimmune responses and promotes immunological tolerance
| Autor: | Thomas Kamradt, Alberto Sanchez-Fueyo, Vijay K. Kuchroo, Orissa Bender, Jane Tian, Jose-Carlos Gutierrez-Ramos, Terry B. Strom, Dominic Picarella, Catherine A. Sabatos, Natasha Manlongat, Anthony J. Coyle, Christoph Domenig, Xin Xiao Zheng |
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| Rok vydání: | 2003 |
| Předmět: |
CD4-Positive T-Lymphocytes
Interleukin 2 Virus genetics Regulatory T cell T cell Immunology Biology Mice Immune system Mice Inbred NOD Immune Tolerance medicine Animals Immunology and Allergy IL-2 receptor Hepatitis A Virus Cellular Receptor 2 Receptors Interleukin-2 Th1 Cells Transplantation medicine.anatomical_structure CTLA-4 Immune System Receptors Virus Signal Transduction medicine.drug |
| Zdroj: | Nature Immunology. 4:1093-1101 |
| ISSN: | 1529-2916 1529-2908 |
| Popis: | Although T helper (T(H)) cell-mediated immunity is required to effectively eliminate pathogens, unrestrained T(H) activity also contributes to tissue injury in many inflammatory and autoimmune diseases. We report here that the T(H) type 1 (T(H)1)-specific Tim-3 (T cell immunoglobulin domain, mucin domain) protein functions to inhibit aggressive T(H)1-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 T(H)1-dependent immune responses and to facilitate the development of immunological tolerance. |
| Databáze: | OpenAIRE |
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