title: Robust Anti-viral Immunity Requires Multiple Distinct T Cell-Dendritic Cell Interactions.
abstract: Host defense against viruses and intracellular parasites depends on effector CD8(+) T cells, whose optimal clonal expansion, differentiation, and memory properties require signals from CD4(+) T cells. Here, we addressed the role of dendritic cell (DC) subsets in initial activation of the two T cell types and their co-operation. Surprisingly, initial priming of CD4(+) and CD8(+) T cells was spatially segregated within the lymph node and occurred on different DCs with temporally distinct patterns of antigen presentation via MHCI versus MHCII molecules. DCs that co-present antigen via both MHC molecules were detected at a later stage; these XCR1(+) DCs are the critical platform involved in CD4(+) T cell augmentation of CD8(+) T cell responses. These findings delineate the complex choreography of cellular interactions underlying effective cell-mediated anti-viral responses, with implications for basic DC subset biology, as well as for translational application to the development of vaccines that evoke optimal T cell immunity.
authors: Institute for Experimental Immunology, University of Bonn, 53105 Bonn, Germany.
authors: Sarah
authors: S
authors: Eickhoff
authors: Institute for Experimental Immunology, University of Bonn, 53105 Bonn, Germany.
authors: Anna
authors: A
authors: Brewitz
authors: Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Michael Y
authors: MY
authors: Gerner
authors: Institute of Pathology, Charité University Hospital Berlin, 10117 Berlin, Germany.
authors: Frederick
authors: F
authors: Klauschen
authors: Institute for Experimental Immunology, University of Bonn, 53105 Bonn, Germany.
authors: Karl
authors: K
authors: Komander
authors: Laboratory for Immune Regulation, World Premier International Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan; Laboratory for Inflammatory Regulation, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan.
authors: Hiroaki
authors: H
authors: Hemmi
authors: Institute for Experimental Immunology, University of Bonn, 53105 Bonn, Germany.
authors: Natalio
authors: N
authors: Garbi
authors: Laboratory for Immune Regulation, World Premier International Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan; Laboratory for Inflammatory Regulation, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan.
authors: Tsuneyasu
authors: T
authors: Kaisho
authors: Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: rgermain@nih.gov.
authors: Ronald Nathan
authors: RN
authors: Germain
authors: Institute for Experimental Immunology, University of Bonn, 53105 Bonn, Germany. Electronic address: wkastenm@uni-bonn.de.
authors: Wolfgang
authors: W
authors: Kastenmüller
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002450:Cell Communication; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D019707:Receptors, Chemokine / Q000235:genetics; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014615:Vaccinia / Q000276:immunology*; D014616:Vaccinia virus / Q000502:physiology*
chemical_list: D000956:Antigens, Viral; D019707:Receptors, Chemokine; C551408:XC chemokine receptor 1, mouse