TIM-4 expressed on APCs induces T cell expansion and survival |
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Authors: | Rodriguez-Manzanet Roselynn Meyers Jennifer Hartt Balasubramanian Savithri Slavik Jacqueline Kassam Nasim Dardalhon Valerie Greenfield Edward A Anderson Ana C Sobel Raymond A Hafler David A Strom Terry B Kuchroo Vijay K |
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Affiliation: | Department of Neurology, Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. |
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Abstract: | TIM (T cell, Ig, mucin) proteins can regulate T cell immune responses. Tim-4 mRNA is not expressed in T cells, but exclusively in APCs. Tim-4 is a ligand for Tim-1 and Tim-4.Ig fusion protein was shown to either inhibit or expand T cells. However, the molecular basis for such opposite effects was not defined. By generating mAbs, we show that expression of Tim-4 protein is restricted to CD11c(+) and CD11b(+) cells and is up-regulated upon activation. We show that Tim-4 specifically phosphorylates Tim-1 and induces T cell expansion by enhancing cell division and reducing apoptosis. Tim-4 also induces the phosphorylation of signaling molecules LAT, Akt, and ERK1/2 in T cells. Tim-4, expressed on APCs, is a costimulatory molecule that promotes T cell expansion and survival by cross-linking Tim-1 on T cells. |
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