1. Splenic CD8α+ dendritic cells undergo rapid programming by cytosolic bacteria and inflammation to induce protective CD8+ T-cell memory
- Author
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Saidi M.Homa Soudja, Grégoire Lauvau, Laura Campisi, Nicolas Glaichenhaus, Frédéric Brau, Anne Lazzari, Frederic Geissmann, Emilie Narni-Mancinelli, Julie Cazareth, Delphine Bassand, Immunologie des maladies infectieuses allergiques et autoimmunes, Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Centre for Cellular and Molecular Biology of Inflammation, King‘s College London, Institut de pharmacologie moléculaire et cellulaire (IPMC), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Department of Microbiology and Immunology, and Albert Einstein College of Medicine [New York]
- Subjects
MESH: Inflammation ,Adoptive cell transfer ,MESH: Spleen ,Priming (immunology) ,Cell Count ,MESH: T-Lymphocyte Subsets ,MESH: Virulence ,CD8-Positive T-Lymphocytes ,MESH: Listeria monocytogenes ,Lymphocyte Activation ,MESH: Membrane Transport Proteins ,Mice ,Cytosol ,0302 clinical medicine ,MESH: Cytosol ,T-Lymphocyte Subsets ,Immunology and Allergy ,Cytotoxic T cell ,MESH: Animals ,Listeriosis ,MESH: Bacterial Proteins ,Cells, Cultured ,Sequence Deletion ,Adenosine Triphosphatases ,Mice, Inbred BALB C ,0303 health sciences ,MESH: Dendritic Cells ,Virulence ,biology ,MESH: Sequence Deletion ,Acquired immune system ,MESH: CD8-Positive T-Lymphocytes ,Adoptive Transfer ,3. Good health ,MESH: Immunologic Memory ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,medicine.symptom ,MESH: Cells, Cultured ,CD8 Antigens ,Immunology ,MESH: Mice, Inbred BALB C ,Inflammation ,03 medical and health sciences ,Bacterial Proteins ,Antigen ,MHC class I ,MESH: Adenosine Triphosphatases ,medicine ,Animals ,MESH: Lymphocyte Activation ,MESH: Mice ,030304 developmental biology ,SecA Proteins ,MESH: Cell Count ,Membrane Transport Proteins ,Dendritic Cells ,Listeria monocytogenes ,MESH: Adoptive Transfer ,MESH: Listeriosis ,biology.protein ,MESH: Antigens, CD8 ,Immunologic Memory ,SEC Translocation Channels ,Spleen ,CD8 ,030215 immunology - Abstract
International audience; Memory CD8(+) T lymphocytes are critical effector cells of the adaptive immune system mediating long-lived pathogen-specific protective immunity. Three signals - antigen, costimulation and inflammation - orchestrate optimal CD8(+) T-cell priming and differentiation into effector and memory cells and shape T-cell functional fate and ability to protect against challenge infections. While among the conventional spleen DCs (cDCs), the CD8α(+) but not the CD8α(-) cDCs most efficiently mediate CD8(+) T-cell priming, it is unclear which subset, irrespective of their capacity to process MHC class I-associated antigens, is most efficient at inducing naïve CD8(+) T-cell differentiation into pathogen-specific protective memory cells in vivo. Moreover, the origin of the required signals is still unclear. Using mice infected with the intracellular bacterium Listeria monocytogenes, we show that splenic CD8α(+) cDCs become endowed with all functional features to optimally prime protective memory CD8(+) T cells in vivo within only a few hours post-immunization. Such programming requires both cytosolic signals resulting from bacterial invasion of the host cells and extracellular inflammatory mediators. Thus, these data designate these cells as the best candidates to facilitate the development of cell-based vaccine therapy.
- Published
- 2011
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