title: Differential requirement for the CD40-CD154 costimulatory pathway during Th cell priming by CD8 alpha+ and CD8 alpha- murine dendritic cell subsets.
abstract: Dendritic cells (DCs) regulate the development of distinct Th populations and thereby provoke appropriate immune responses to various kinds of Ags. In the present work, we investigated the role CD40-CD154 interactions play during the process of Th cell priming by CD8 alpha(+) and CD8 alpha(-) murine DC subsets, which have been reported to differently regulate the Th response. Adoptive transfer of Ag-pulsed CD8 alpha(+) DCs induced a Th1 response and the production of IgG2a Abs, whereas transfer of CD8 alpha(-) DCs induced Th2 cells and IgE Abs in vivo. Induction of distinct Th populations by each DC subset was also confirmed in vitro. Although interruption of CD80/CD86-CD28 interactions inhibited Th cell priming by both DC subsets, disruption of CD40-CD154 interactions only inhibited the induction of the Th1 response by CD8 alpha(+) DCs in vivo. CD40-CD154 interactions were not required for the proliferation of Ag-specific naive Th cells stimulated by either DC subset, but were indispensable in the production of IL-12 from CD8 alpha(+) DCs and their induction of Th1 cells in vitro. Taken together, in our immunization model of Ag-pulsed DC transfer, CD40-CD154 interactions play an important role in the development of CD8 alpha(+) DC-driven Th1 responses but not CD8 alpha(-) DC-driven Th2 responses to protein Ags.
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yasumi
authors.forename: Kenji
authors.initials: K
authors.lastname: Katamura
authors.forename: Takakazu
authors.initials: T
authors.lastname: Yoshioka
authors.forename: Taka-aki
authors.initials: TA
authors.lastname: Meguro
authors.forename: Ryuta
authors.initials: R
authors.lastname: Nishikomori
authors.forename: Toshio
authors.initials: T
authors.lastname: Heike
authors.forename: Manabu
authors.initials: M
authors.lastname: Inobe
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Kon
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Uede
authors.forename: Tatsutoshi
authors.initials: T
authors.lastname: Nakahata
mesh_terms: D000818:Animals; D019013:CD40 Antigens / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D023201:CD40 Ligand / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D016827:CD8 Antigens / Q000096:biosynthesis* / Q000378:metabolism; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015398:Signal Transduction / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology
chemical_list: D019013:CD40 Antigens; D016827:CD8 Antigens; C431698:CD8alpha antigen; D016207:Cytokines; D023201:CD40 Ligand