The role of the LAT-PLC-gamma1 interaction in T regulatory cell function.
The role of the LAT-PLC-gamma1 interaction in T regulatory cell function.
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DOI：
10.4049/jimmunol.0902876
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发表时间：
2010-03-01
期刊：
影响因子：
--
通讯作者：
Zhang W
中科院分区：
文献类型：
--
作者：
Chuck MI;Zhu M;Shen S;Zhang W
The interaction between the linker for activation of T cells (LAT) with phospholipase C (PLC-γ1) is important for T cell receptor (TCR)-mediated Ca2+ signaling and MAPK activation. Knock-in mice harboring a mutation at the PLC-γ1 binding site (Y136) of LAT develop a severe lymphoproliferative syndrome. These mice have defective thymic development and selection and lack natural regulatory T cells, implicating a breakdown of both central and peripheral tolerance. To bypass this developmental defect, we developed a conditional knock-in line in which only LATY136F is expressed in mature T cells after deletion of the wildtype LAT allele. Analysis of LATY136F T cells indicated that the interaction between LAT and PLC-γ1 plays an important role in TCR-mediated signaling, proliferation, and IL-2 production. Furthermore, the deletion of LAT induced development of the lymphoproliferative syndrome in these mice. Although Foxp3+ natural Treg cells were present in these mice after deletion, they were unable to suppress the proliferation of conventional T cells. Our data indicated that the binding of LAT to PLC-γ1 is essential for the suppressive function of CD4+CD25+ regulatory T cells.
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影响因子：
30.5
作者：
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通讯作者：
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DOI：
10.1084/jem.20081811
发表时间：
2009-02-16
期刊：
The Journal of experimental medicine
影响因子：
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作者：
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影响因子：
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作者：
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30.5
作者：
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