title: Provision of continuous maturation signaling to dendritic cells by RIG-I-stimulating cytosolic RNA synthesis of Sendai virus.
abstract: Dendritic cell (DC)-based immunotherapy has potential for treating infections and malignant tumors, but the functional capacity of DC must be assessed in detail, especially maturation and Ag-specific CTL priming. Recent reports suggest that DC that are provided with continuous maturation signals in vivo after transfer into patients are required to elicit the full DC functions. We demonstrate in this study that the rSendai virus vector (SeV) is a novel and ideal stimulant, providing DC with a continuous maturation signal via viral RNA synthesis in the cytosol, resulting in full maturation of monocyte-derived DC(s). Both RIG-I-dependent cytokine production and CD4 T cell responses to SeV-derived helper Ags are indispensable for overcoming regulatory T cell suppression to prime melanoma Ag recognized by T cell-1-specific CTL in the regulatory T cell abundant setting. DC stimulated via cytokine receptors, or TLRs, do not show these functional features. Therefore, SeV-infected DC have the potential for DC-directed immunotherapy.
authors.affiliation: Division of Pathophysiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. okap@surg2.med.kyushu-u.ac.jp
authors.forename: Shinji
authors.initials: S
authors.lastname: Okano
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Yonemitsu
authors.forename: Ken
authors.initials: K
authors.lastname: Shirabe
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kakeji
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
authors.forename: Mamoru
authors.initials: M
authors.lastname: Harada
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Yoshikai
authors.forename: Makoto
authors.initials: M
authors.lastname: Inoue
authors.forename: Mamoru
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Katsuo
authors.initials: K
authors.lastname: Sueishi
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology; D000956:Antigens, Viral / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002461:Cell Line, Transformed; D018920:Coculture Techniques; D003600:Cytosol / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D003601:Cytotoxicity Tests, Immunologic; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000502:physiology*; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology / Q000821:virology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D006801:Humans; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D012367:RNA, Viral / Q000096:biosynthesis* / Q000235:genetics; D011971:Receptors, Immunologic; D029082:Sendai virus / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism / Q000821:virology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism / Q000821:virology; D014779:Virus Replication / Q000235:genetics / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D012367:RNA, Viral; D011971:Receptors, Immunologic; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases