title: The requirement of linker for activation of T cells in the primary and memory responses of CD8 T cells.
abstract: 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.
authors: Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
authors: Chih-wen
authors: CW
authors: Ou-Yang
authors: Minghua
authors: M
authors: Zhu
authors: Sarah A
authors: SA
authors: Sullivan
authors: Deirdre M
authors: DM
authors: Fuller
authors: Weiguo
authors: W
authors: Zhang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000008:administration & dosage / Q000172:deficiency / Q000502:physiology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory / Q000235:genetics; D008088:Listeriosis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D008565:Membrane Proteins / Q000008:administration & dosage / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010750:Phosphoproteins / Q000008:administration & dosage / Q000172:deficiency / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C491734:Lat protein, mouse; D008565:Membrane Proteins; D010750:Phosphoproteins
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