Plasmacytoid dendritic cells regulate Th cell responses through OX40 ligand and type I IFNs.
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.
Ito
Tomoki
T
First Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
Amakawa
Ryuichi
R
Inaba
Muneo
M
Hori
Toshiyuki
T
Ota
Maiko
M
Nakamura
Kengo
K
Takebayashi
Masashi
M
Miyaji
Michihiko
M
Yoshimura
Tomoo
T
Inaba
Kayo
K
Fukuhara
Shirou
S
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*
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