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The costimulatory role of TIM molecules
Authors:Authors' addressesRoselynn Rodriguez-Manzanet  Rosemarie DeKruyff  Vijay K. Kuchroo  Dale T. Umetsu
Affiliation:Department of Neurology, Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.;
Children's Hospital Boston, Division of Immunology and Allergy, Harvard Medical School, Boston, MA, USA.
Abstract:Summary:  The T-cell immunoglobulin domain and mucin domain (TIM) family, including TIM-1, TIM-2, TIM-3, and TIM-4, is a relatively newly described group of molecules with a conserved structure and important immunological functions, including T-cell activation, induction of T-cell apoptosis and T-cell tolerance, and the clearance of apoptotic cells. TIM-1 costimulates T-cell activation and enhances cytokine production. In humans, TIM-1 also serves as a susceptibility gene for allergy and asthma. TIM-3, expressed on T cells and dendritic cells, regulates T-cell apoptosis and immune tolerance. By contrast, TIM-4, which is expressed primarily on antigen-presenting cells and which is a receptor for phosphatidylserine, regulates T-cell activation and tolerance, in part by mediating the uptake and engulfment of apoptotic cells. The TIM molecules thus have surprisingly broad activities affecting multiple aspects of immunology.
Keywords:TIM    costimulation    T-cell    allergy    tolerance    autoimmunity
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