Article: article d'un périodique ou d'un magazine.
Essential role of the Wnt pathway effector Tcf-1 for the establishment of functional CD8 T cell memory.
Proceedings of the National Academy of Sciences of the United States of America
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Immune protection from intracellular pathogens depends on the generation of terminally differentiated effector and of multipotent memory precursor CD8 T cells, which rapidly regenerate effector and memory cells during recurrent infection. The identification of factors and pathways involved in CD8 T cell differentiation is of obvious importance to improve vaccination strategies. Here, we show that mice lacking T cell factor 1 (Tcf-1), a nuclear effector of the canonical Wingless/Integration 1 (Wnt) signaling pathway, mount normal effector and effector memory CD8 T cell responses to infection with lymphocytic choriomeningitis virus (LCMV). However, Tcf-1-deficient CD8 T cells are selectively impaired in their ability to expand upon secondary challenge and to protect from recurrent virus infection. Tcf-1-deficient mice essentially lack CD8 memory precursor T cells, which is evident already at the peak of the primary response, suggesting that Tcf-1 programs CD8 memory cell fate. The function of Tcf-1 to establish CD8 T cell memory is dependent on the catenin-binding domain in Tcf-1 and requires the Tcf-1 coactivators and Wnt signaling intermediates beta-catenin and gamma-catenin. These findings demonstrate that the canonical Wnt signaling pathway plays an essential role for CD8 central memory T cell differentiation under physiological conditions in vivo. They raise the possibility that modulation of Wnt signaling may be exploited to improve the generation of CD8 memory T cells during vaccination or for therapies designed to promote sustained cytotoxic CD8 T cell responses against tumors.
Animals, CD8-Positive T-Lymphocytes/cytology, CD8-Positive T-Lymphocytes/immunology, Cell Proliferation, Immunologic Memory, Lymphocytic choriomeningitis virus/immunology, Mice, Mice, Inbred C57BL, Protein Binding, Signal Transduction, T Cell Transcription Factor 1/deficiency, T Cell Transcription Factor 1/immunology, Wnt Proteins/metabolism, beta Catenin/immunology, beta Catenin/metabolism, gamma Catenin/immunology, gamma Catenin/metabolism
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