title: CD8+T Cells Orchestrate pDC-XCR1+Dendritic Cell Spatial and Functional Cooperativity to Optimize Priming.
abstract: Adaptive cellular immunity is initiated by antigen-specific interactions between T lymphocytes and dendritic cells (DCs). Plasmacytoid DCs (pDCs) support antiviral immunity by linking innate and adaptive immune responses. Here we examined pDC spatiotemporal dynamics during viral infection to uncover when, where, and how they exert their functions. We found that pDCs accumulated at sites of CD8+T cell antigen-driven activation in a CCR5-dependent fashion. Furthermore, activated CD8+T cells orchestrated the local recruitment of lymph node-resident XCR1 chemokine receptor-expressing DCs via secretion of the XCL1 chemokine. Functionally, this CD8+T cell-mediated reorganization of the local DC network allowed for the interaction and cooperation of pDCs and XCR1+DCs, thereby optimizing XCR1+DC maturation and cross-presentation. These data support a model in which CD8+T cells upon activation create their own optimal priming microenvironment by recruiting additional DC subsets to the site of initial antigen recognition.
authors.affiliation: Institute of Experimental Immunology, University Hospital, University of Bonn, 53127 Bonn, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Brewitz
authors.affiliation: Institute of Experimental Immunology, University Hospital, University of Bonn, 53127 Bonn, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Eickhoff
authors.affiliation: Institute of Experimental Immunology, University Hospital, University of Bonn, 53127 Bonn, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Dähling
authors.affiliation: Molecular Immunology and Cell Biology, Life and Medical Sciences Institute, University of Bonn, 53115 Bonn, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Quast
authors.affiliation: Department of Microbiology and Immunology, The University of Melbourne, Peter Doherty Institute for Infection and Immunity, Parkville,VIC 3010, Australia.
authors.forename: Sammy
authors.initials: S
authors.lastname: Bedoui
authors.affiliation: Molecular Immunology, Robert-Koch-Institute, 13353 Berlin, Germany.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kroczek
authors.affiliation: Institute of Experimental Immunology, University Hospital, University of Bonn, 53127 Bonn, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Kurts
authors.affiliation: Institute of Experimental Immunology, University Hospital, University of Bonn, 53127 Bonn, Germany.
authors.forename: Natalio
authors.initials: N
authors.lastname: Garbi
authors.affiliation: Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital, University of Bonn, 53127 Bonn, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: Barchet
authors.affiliation: Division of Immunology, Transplantation and Infectious Diseases and Experimental Imaging Center, IRCCS San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Via Olgettina 58, Milan 20132, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Iannacone
authors.affiliation: Institute of Pathology, Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany; Einstein Foundation Berlin, 10117 Berlin, Germany.
authors.forename: Frederick
authors.initials: F
authors.lastname: Klauschen
authors.affiliation: Molecular Immunology and Cell Biology, Life and Medical Sciences Institute, University of Bonn, 53115 Bonn, Germany.
authors.forename: Waldemar
authors.initials: W
authors.lastname: Kolanus
authors.affiliation: Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Wakayama 641-8509, Japan; Laboratory for Inflammatory Regulation, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan; Laboratory for Immune Regulation, World Premier International Research Center Initiative, Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Tsuneyasu
authors.initials: T
authors.lastname: Kaisho
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63108, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Colonna
authors.affiliation: Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892-0421, USA.
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Germain
authors.affiliation: Institute of Experimental Immunology, University Hospital, University of Bonn, 53127 Bonn, Germany. Electronic address: wkastenm@uni-bonn.de.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kastenmüller
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D051379:Mice; D008822:Mice, Transgenic
keywords: CCL3; CCL4; CCR5; CXCR3; XCL1; chemokine; cooperation; migration; spatiotemporal; viral infection