The requirement of LAT in the primary and memory responses of CD8 T cells

• Published in: The Journal of immunology (1950) 2013-02, Vol.190 (6), p.2938-2947
• Main Authors: Ou-Yang, Chih-wen, Zhu, Minghua, Sullivan, Sarah A, Fuller, Deirdre M., Zhang, Weiguo
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1203163

Linker for activation of T cells (LAT) is a transmembrane adaptor protein that links T cell receptor (TCR) engagement to downstream signaling events. While 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 antigen-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, while it is dispensable for contraction and memory maintenance, TCR-mediated signaling regulates CD8 T cell memory differentiation and is essential for the memory response against pathogens.