title: Splenic CD8α⁺ dendritic cells undergo rapid programming by cytosolic bacteria and inflammation to induce protective CD8⁺ T-cell memory.
abstract: 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.
authors.affiliation: Institut National de Santé et de Recherche Médicale Unité 924, Groupe Avenir, Valbonne, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Campisi
authors.forename: Saidi M'Homa
authors.initials: SM
authors.lastname: Soudja
authors.forename: Julie
authors.initials: J
authors.lastname: Cazareth
authors.forename: Delphine
authors.initials: D
authors.lastname: Bassand
authors.forename: Anne
authors.initials: A
authors.lastname: Lazzari
authors.forename: Frédéric
authors.initials: F
authors.lastname: Brau
authors.forename: Emilie
authors.initials: E
authors.lastname: Narni-Mancinelli
authors.forename: Nicolas
authors.initials: N
authors.lastname: Glaichenhaus
authors.forename: Frédéric
authors.initials: F
authors.lastname: Geissmann
authors.forename: Grégoire
authors.initials: G
authors.lastname: Lauvau
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D019264:Adoptive Transfer; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D016827:CD8 Antigens / Q000276:immunology / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D002452:Cell Count; D002478:Cells, Cultured; D003600:Cytosol / Q000276:immunology / Q000382:microbiology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D007156:Immunologic Memory; D007249:Inflammation; D008089:Listeria monocytogenes / Q000235:genetics / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D008088:Listeriosis / Q000276:immunology* / Q000382:microbiology; D008213:Lymphocyte Activation; D026901:Membrane Transport Proteins / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D000069816:SEC Translocation Channels; D000081416:SecA Proteins; D017384:Sequence Deletion / Q000235:genetics; D013154:Spleen / Q000382:microbiology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D014774:Virulence / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D016827:CD8 Antigens; C431698:CD8alpha antigen; D026901:Membrane Transport Proteins; D000069816:SEC Translocation Channels; D000251:Adenosine Triphosphatases; D000081416:SecA Proteins