The requirement of linker for activation of T cells in the primary and memory responses of CD8 T cells.

Journal Article

Linker for activation of T cells (LAT) is a transmembrane adaptor protein that links TCR engagement to downstream signaling events. Although it is clear that LAT is essential in thymocyte development and initiation of T cell activation, its function during T cell expansion, contraction, and memory formation remains unknown. To study the role of TCR-mediated signaling in CD8 T cells during the course of pathogen infection, we used an inducible mouse model to delete LAT in Ag-specific CD8 T cells at different stages of Listeria infection and analyzed the effect of deletion on T cell responses. Our data showed that LAT is important for maintaining CD8 T cell expansion during the priming phase; however, it is not required for CD8 T cell contraction and memory maintenance. Moreover, LAT deficiency accelerates memory differentiation during the effector-to-memory transition, leading to a higher frequency of KLRG1(low)IL-7R(high)CD62L(high) memory T cells. Nonetheless, these LAT-deficient memory T cells were unable to proliferate or produce cytokines upon secondary infection. Our data demonstrated that, although TCR-mediated signaling is dispensable for contraction and memory maintenance, it regulates CD8 T cell memory differentiation and is essential for the memory response against pathogens.

Full Text

Duke Authors

Cited Authors

  • Ou-Yang, C-W; Zhu, M; Sullivan, SA; Fuller, DM; Zhang, W

Published Date

  • March 15, 2013

Published In

Volume / Issue

  • 190 / 6

Start / End Page

  • 2938 - 2947

PubMed ID

  • 23401587

Electronic International Standard Serial Number (EISSN)

  • 1550-6606

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.1203163

Language

  • eng

Conference Location

  • United States