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Roselynn Rodriguez-Manzanet, Jennifer Hartt Meyers, Savithri Balasubramanian, Jacqueline Slavik, Nasim Kassam, Valerie Dardalhon, Edward A Greenfield, Ana C Anderson, Raymond A Sobel, David A Hafler, Terry B Strom, Vijay K Kuchroo, TIM-4 Expressed on APCs Induces T Cell Expansion and Survival, The Journal of Immunology, Volume 180, Issue 7, April 2008, Pages 4706–4713, https://doi.org/10.4049/jimmunol.180.7.4706
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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.