LAT Plays Important Role in Thymocyte Survival and Mature T Cell Activation (87.35)

Abstract

Abstract LAT (Linker for Activation of T-cells) is a membrane-associated adaptor protein that plays a critical role in linking T-cell receptor engagement to activation of its downstream signaling events. Upon tyrosine phosphorylation, LAT binds Grb2, Gads, and PLC-gamma1. Previous studies show that LAT is essential in thymocyte development as LAT-deficient mice completely lack mature T cells. In addition, LAT-deficient Jurkat cells have a severe defect in TCR-mediated signaling. In order to investigate the role of LAT in T cell activation, survival, and homeostasis, mice in which the LAT gene can be inducibly deleted from thymocytes and mature T cells by injection of tamoxifen were generated. Our data showed that tamoxifen treatment of these mice led to a dramatic loss of thymocytes, especially DP thymocytes. Deletion of LAT in mature T cells affected TCR-mediated signaling, IL-2 production, and proliferation. These data suggested that LAT plays an important role in thymocyte survival and TCR-mediated signaling in mature T cells.