title: Imaging of the cross-presenting dendritic cell subsets in the skin-draining lymph node.
abstract: Dendritic cells (DCs) are antigen-presenting cells specialized for activating T cells to elicit effector T-cell functions. Cross-presenting DCs are a DC subset capable of presenting antigens to CD8(+) T cells and play critical roles in cytotoxic T-cell-mediated immune responses to microorganisms and cancer. Although their importance is known, the spatiotemporal dynamics of cross-presenting DCs in vivo are incompletely understood. Here, we study the T-cell zone in skin-draining lymph nodes (SDLNs) and find it is compartmentalized into regions for CD8(+) T-cell activation by cross-presenting DCs that express the chemokine (C motif) receptor 1 gene, Xcr1 and for CD4(+) T-cell activation by CD11b(+) DCs. Xcr1-expressing DCs in the SDLNs are composed of two different populations: migratory (CD103(hi)) DCs, which immigrate from the skin, and resident (CD8α(hi)) DCs, which develop in the nodes. To characterize the dynamic interactions of these distinct DC populations with CD8(+) T cells during their activation in vivo, we developed a photoconvertible reporter mouse strain, which permits us to distinctively visualize the migratory and resident subsets of Xcr1-expressing DCs. After leaving the skin, migratory DCs infiltrated to the deep T-cell zone of the SDLNs over 3 d, which corresponded to their half-life in the SDLNs. Intravital two-photon imaging showed that after soluble antigen immunization, the newly arriving migratory DCs more efficiently form sustained conjugates with antigen-specific CD8(+) T cells than other Xcr1-expressing DCs in the SDLNs. These results offer in vivo evidence for differential contributions of migratory and resident cross-presenting DCs to CD8(+) T-cell activation.
authors.affiliation: Laboratory for Tissue Dynamics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan; Translational Imaging Center, University of Southern California, Los Angeles, CA 90089;
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kitano
authors.affiliation: Laboratory for Host Defense, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan; Department of Allergy and Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan; Department of Immunology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Okayama 700-8558, Japan;
authors.forename: Chihiro
authors.initials: C
authors.lastname: Yamazaki
authors.affiliation: Laboratory for Tissue Dynamics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan;
authors.forename: Akiko
authors.initials: A
authors.lastname: Takumi
authors.affiliation: Laboratory for Tissue Dynamics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan; Laboratory of Lymphocyte Differentiation, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan;
authors.forename: Takashi
authors.initials: T
authors.lastname: Ikeno
authors.affiliation: Laboratory for Host Defense, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan; Laboratory for Inflammatory Regulation, RIKEN Center for Integrative Medical Sciences, 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; Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Wakayama 641-8509, Japan;
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hemmi
authors.affiliation: Laboratory for Tissue Dynamics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan;
authors.forename: Noriko
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: Laboratory for Immunotherapy, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan;
authors.forename: Kanako
authors.initials: K
authors.lastname: Shimizu
authors.affiliation: Translational Imaging Center, University of Southern California, Los Angeles, CA 90089;
authors.forename: Scott E
authors.initials: SE
authors.lastname: Fraser
authors.affiliation: Laboratory for Host Defense, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan; Laboratory for Inflammatory Regulation, RIKEN Center for Integrative Medical Sciences, 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; Department of Immunology, Faculty of Medicine, Kagawa University, Miki, Kagawa 761-0793, Japan;
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Hoshino
authors.affiliation: Laboratory for Host Defense, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan; Department of Allergy and Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan; Laboratory for Inflammatory Regulation, RIKEN Center for Integrative Medical Sciences, 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; Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Wakayama 641-8509, Japan; takaharu.okada@riken.jp tkaisho@wakayama-med.ac.jp.
authors.forename: Tsuneyasu
authors.initials: T
authors.lastname: Kaisho
authors.affiliation: Laboratory for Tissue Dynamics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan; Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Saitama, Saitama 332-0012, Japan; Graduate School of Medical Life Science, Yokohama City University, Yokohama 230-0045, Japan takaharu.okada@riken.jp tkaisho@wakayama-med.ac.jp.
authors.forename: Takaharu
authors.initials: T
authors.lastname: Okada
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002465:Cell Movement; D045142:Cross-Priming; D003713:Dendritic Cells / Q000276:immunology*; D007114:Immunization; D039001:Integrin alpha Chains / Q000032:analysis; D008198:Lymph Nodes / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019707:Receptors, Chemokine / Q000032:analysis / Q000502:physiology; D012867:Skin / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D039001:Integrin alpha Chains; D019707:Receptors, Chemokine; C551408:XC chemokine receptor 1, mouse; C091367:alpha E integrins
keywords: CD8+ T cell; cross-presentation; dendritic cell; intravital two-photon imaging; photoconversion