The importance of LAT in the activation, homeostasis, and regulatory function of T cells.

Published

Journal Article

LAT (linker for activation of T cells) is a transmembrane adaptor protein that plays an essential role in TCR-mediated signaling and thymocyte development. Because LAT-deficient mice have an early block in thymocyte development, we utilized an inducible system to delete LAT in primary T cells to study LAT function in T cell activation, homeostasis, and survival. Deletion of LAT caused primary T cells to become unresponsive to stimulation from the TCR and impaired T cell homeostatic proliferation and long term survival. Furthermore, deletion of LAT led to reduced expression of Foxp3, CTLA-4, and CD25 in T(reg) cells and impaired their function. Consequently, mice with LAT deleted developed a lymphoproliferative syndrome similar to that in LATY136F mice, although less severe. Our data implicate that LAT has positive and negative roles in the regulation of mature T cells.

Full Text

Duke Authors

Cited Authors

  • Shen, S; Chuck, MI; Zhu, M; Fuller, DM; Yang, C-WO; Zhang, W

Published Date

  • November 2010

Published In

Volume / Issue

  • 285 / 46

Start / End Page

  • 35393 - 35405

PubMed ID

  • 20837489

Pubmed Central ID

  • 20837489

Electronic International Standard Serial Number (EISSN)

  • 1083-351X

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.M110.145052

Language

  • eng