title: Plasmacytoid dendritic cells regulate Th cell responses through OX40 ligand and type I IFNs.
abstract: Dendritic cells (DCs) show a functional plasticity in determining Th responses depending on their maturational stage or on maturational signals delivered to the DCs. Human plasmacytoid DCs (PDCs) can induce either Th1- or Th2-type immune responses upon exposure to viruses or IL-3, respectively. In this study we have investigated the Th-polarizing capacity of PDCs after short (24-h) or long (72-h) culture with stimuli and have assessed the expression and function of OX40 ligand (OX40L) in PDC-mediated Th polarization in addition to type I IFN-dependent responses. IL-3-treated PDCs expressed OX40L, but produced almost no IFN-alpha in response to T cell stimulation (CD40 ligand or T cell interaction), resulting in the preferential priming of Th2 cells through OX40L-dependent mechanisms. Meanwhile, PDCs were rapidly endowed by viral infection (Sendai virus) with a high potency to develop IFN-gamma-producing Th cells depending on their capacity to residually produce IFN-alpha. Although Sendai virus-stimulated PDCs simultaneously expressed OX40L in their maturational process, the Th1-inducing effect of endogenous type I IFNs may overcome and thus conceal the OX40L-dependent Th2 responses. However, during maturation in response to Sendai virus over the longer 72-h period, the expression level of OX40L was up-regulated, whereas the residual IFN-alpha-producing ability was down-regulated, and consequently, the PDCs with prolonged Sendai virus stimulation induced Th2 responses to some extent. Thus, PDCs have the distinct means to dictate an appropriate response to environmental stimuli.
authors.affiliation: First Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Ito
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Amakawa
authors.forename: Muneo
authors.initials: M
authors.lastname: Inaba
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Hori
authors.forename: Maiko
authors.initials: M
authors.lastname: Ota
authors.forename: Kengo
authors.initials: K
authors.lastname: Nakamura
authors.forename: Masashi
authors.initials: M
authors.lastname: Takebayashi
authors.forename: Michihiko
authors.initials: M
authors.lastname: Miyaji
authors.forename: Tomoo
authors.initials: T
authors.lastname: Yoshimura
authors.forename: Kayo
authors.initials: K
authors.lastname: Inaba
authors.forename: Shirou
authors.initials: S
authors.lastname: Fukuhara
mesh_terms: D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007370:Interferon Type I / Q000502:physiology*; D016898:Interferon-alpha / Q000096:biosynthesis; D018793:Interleukin-13 / Q000378:metabolism; D007377:Interleukin-3 / Q000502:physiology; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008024:Ligands; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000502:physiology*; D053278:OX40 Ligand; D029082:Sendai virus / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism*
chemical_list: D016207:Cytokines; D007370:Interferon Type I; D016898:Interferon-alpha; D018793:Interleukin-13; D007377:Interleukin-3; D015848:Interleukin-5; D008024:Ligands; D008562:Membrane Glycoproteins; D053278:OX40 Ligand; C089251:TNFSF4 protein, human; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D015847:Interleukin-4