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

• Published in: The Journal of immunology (1950) 2013-03, 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
• Subjects: Adaptor Proteins, Signal Transducing - administration & dosage; Adaptor Proteins, Signal Transducing - deficiency; Adaptor Proteins, Signal Transducing - physiology; Animals; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - pathology; Cell Differentiation - genetics; Cell Differentiation - immunology; Immunologic Memory - genetics; Listeria; Listeriosis - genetics; Listeriosis - immunology; Listeriosis - pathology; Lymphocyte Activation - genetics; Lymphocyte Activation - immunology; Membrane Proteins - administration & dosage; Membrane Proteins - deficiency; Membrane Proteins - physiology; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Phosphoproteins - administration & dosage; Phosphoproteins - deficiency; Phosphoproteins - physiology; Signal Transduction - genetics; Signal Transduction - immunology; T-Lymphocyte Subsets - cytology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1203163

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.