The role of LAT-PLCγ1 interaction in γδ T cell development and homeostasis.
The role of LAT-PLCγ1 interaction in γδ T cell development and homeostasis.
复制标题
DOI：
10.4049/jimmunol.1302493
复制
发表时间：
2014-03-15
期刊：
影响因子：
--
通讯作者：
Zhang W
中科院分区：
文献类型：
--
作者：
Sullivan SA;Zhu M;Bao S;Lewis CA;Ou-Yang CW;Zhang W
Linker for Activation of T cells, LAT, is a transmembrane adaptor protein 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 PLCγ1 through its four distal tyrosine residues. Mutation of one of these tyrosines, Y136, abolishes LAT binding to PLCγ1. This results in impaired TCR-mediated calcium mobilization and Erk activation. CD4 αβ T cells in LATY136F knock-in mice undergo uncontrolled expansion, causing a severe autoimmune syndrome. In this study, we investigated the importance of the LAT-PLCγ1 interaction in γδ T cells by crossing LATY136F mice with TCRβ−/− mice. Our data showed that the LATY136F mutation had no major effect on homeostasis of epithelial γδ T cells, which could be found in the skin and small intestine. Interestingly, a population of CD4+ γδ 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 αβ T cells in LATY136F mice. Development of these hyperproliferative γδ T cells was not dependent on MHC class II expression or CD4, and their proliferation could in part be suppressed by regulatory T cells. Our data indicated that a unique subset of CD4 γδ T cells can hyperproliferate in LATY136F mice and suggested that LAT-PLCγ1 signaling may function differently in various subsets of γδ T cells.
登录
查看更多内容
影响因子：
3.7
作者：
Fuller DM;Zhu M;Song X;Ou-Yang CW;Sullivan SA;Stone JC;Zhang W
通讯作者：
Zhang W
影响因子：
64.8
作者：
MOMBAERTS, P;CLARKE, AR;TONEGAWA, S
通讯作者：
TONEGAWA, S
影响因子：
20.3
作者：
Qi, Qian;Xia, Mingcan;August, Avery
通讯作者：
August, Avery
影响因子：
56.9
作者：
Sommers, CL;Park, CS;Love, PE
通讯作者：
Love, PE
影响因子：
32.4
作者：
Passoni, L;Hoffman, ES;Hayday, AC
通讯作者：
Hayday, AC