Interferon-gamma production by human cord blood monocyte-derived dendritic cells.
Interferon (IFN)-gamma is produced by T cells and natural killer cells and activates monocytes and dendritic cells (DCs). Recently, IFN-gamma has been shown to be produced by mouse DCs following stimulation with interleukin (IL)-12, which is markedly augmented by the addition of IL-18. We here analyzed whether human DCs secrete IFN-gamma in response to IL-12 and/or IL-18. Human immature DCs, generated from cord blood CD14(+) monocytes by treating with granulocyte-macrophage colony-stimulating factor and IL-4, were incubated with IL-12 and/or IL-18 and assayed for IFN-gamma production. IL-12, but not IL-18, weakly induced IFN-gamma production, while IL-12 together with IL-18 induced high levels of IFN-gamma production. Similar results were obtained with mature DCs, although levels of IFN-gamma production were less than those in immature DCs. Also with mature and immature DCs, IL-12 upregulated the expression of IL-18 receptor alpha (Ralpha), and costimulation with IL-12 and IL-18 upregulated CD40 expression. Anti-IL-18Ralpha antibody abrogated both the IFN-gamma induction and the CD40 upregulation by IL-12 plus IL-18. These findings suggest that IL-12 upregulates IL-18Ralpha expression on human DCs and acts synergistically with IL-18 to induce high levels of IFN-gamma, which subsequently enhances CD40 expression on DCs in an autocrine manner.
Yamaguchi
Nobuko
N
Division of Hematology and Oncology, Department of Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, 663-8501, Japan.
Fujimori
Yoshihiro
Y
Fujibayashi
Yuka
Y
Kasumoto
Ikuyo
I
Okamura
Haruki
H
Nakanishi
Kenji
K
Hara
Hiroshi
H
D019898:Autocrine Communication / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D005312:Fetal Blood / Q000166:cytology / Q000502:physiology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D018121:Receptors, Cytokine / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000378:metabolism
D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D018121:Receptors, Cytokine; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor