1. TLR2 Engagement on CD8 T Cells Enables Generation of Functional Memory Cells in Response to a Suboptimal TCR Signal
- Author
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Anne Cottalorda, Charles-Antoine Coupet, Blandine C. Mercier, Jacqueline Marvel, Nathalie Bonnefoy-Berard, Immunité infection vaccination (I2V), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), and Fargeot, Alexandra
- Subjects
Adoptive cell transfer ,[SDV.IMM] Life Sciences [q-bio]/Immunology ,MESH: Mice, Transgenic ,Blotting, Western ,Immunology ,Receptors, Antigen, T-Cell ,Mice, Transgenic ,MESH: Flow Cytometry ,CD8-Positive T-Lymphocytes ,Biology ,Lymphocyte Activation ,Mice ,Phosphatidylinositol 3-Kinases ,03 medical and health sciences ,0302 clinical medicine ,Antigen ,Animals ,MESH: Blotting, Western ,Immunology and Allergy ,Cytotoxic T cell ,MESH: Animals ,IL-2 receptor ,MESH: Lymphocyte Activation ,MESH: Mice ,030304 developmental biology ,0303 health sciences ,Innate immune system ,T-cell receptor ,MESH: Toll-Like Receptor 2 ,MESH: Receptors, Antigen, T-Cell ,MESH: 1-Phosphatidylinositol 3-Kinase ,Flow Cytometry ,Acquired immune system ,Adoptive Transfer ,MESH: CD8-Positive T-Lymphocytes ,Toll-Like Receptor 2 ,Cell biology ,MESH: Adoptive Transfer ,TLR2 ,MESH: Immunologic Memory ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Immunologic Memory ,030215 immunology - Abstract
TLR are involved in the detection of microbial infection as well as endogenous ligands that signal tissue and cell damage in mammals. This recognition plays an essential role in innate immune response and the initiation of adaptive immune response. We have previously shown that murine CD8 T cells express TLR2, and that costimulation of Ag-activated CD8 T cells with TLR2 ligands enhances their proliferation, survival, and effector functions. We also demonstrated that TLR2 engagement on CD8 T cells significantly reduces their need for costimulatory signals delivered by APC. We show in this study that TLR2 engagement on CD8 T cells lowers the Ag concentration required for optimal activation, and converts a partial activation into a productive process leading to a significant expansion of cells. Using altered peptide ligands, we demonstrate that TLR2 engagement increases CD8 T cell activation and enables the generation of functional memory cells in response to a low TCR signal. This increased activation is associated with an augmented activation of the PI3K. Taken together, our results demonstrate that TLR2 engagement on CD8 T cells lowers their activation threshold for TCR signal strength and enables efficient memory cell generation in response to a weak TCR signal.
- Published
- 2009