The role of LAT-PLC?1 interaction in ?? T cell development and homeostasis.

ABSTRACT: LAT is a transmembrane adaptor protein that is vital for integrating TCR-mediated signals to modulate T cell development, activation, and proliferation. Upon T cell activation, LAT is phosphorylated and associates with Grb2, Gads, and PLC?1 through its four distal tyrosine residues. Mutation of one of these tyrosines, Y136, abolishes LAT binding to PLC?1. This results in impaired TCR-mediated calcium mobilization and Erk activation. CD4 ?? T cells in LATY136F knock-in mice undergo uncontrolled expansion, resulting in a severe autoimmune syndrome. In this study, we investigated the importance of the LAT-PLC?1 interaction in ?? T cells by crossing LATY136F mice with TCR?(-/-) mice. Our data showed that the LATY136F mutation had no major effect on homeostasis of epithelial ?? T cells, which could be found in the skin and small intestine. Interestingly, a population of CD4(+) ?? T cells in the spleen and lymph nodes underwent continuous expansion and produced elevated amounts of IL-4, resulting in an autoimmune syndrome similar to that caused by ?? T cells in LATY136F mice. Development of these hyperproliferative ?? T cells was not dependent on MHC class II expression or CD4, and their proliferation could be suppressed, in part, by regulatory T cells. Our data indicated that a unique subset of CD4 ?? T cells can hyperproliferate in LATY136F mice and suggested that LAT-PLC?1 signaling may function differently in various subsets of ?? T cells.

SUBMITTER: Sullivan SA 

PROVIDER: S-EPMC3951746 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature