title: Regulation of development of CD56 bright CD11c + NK-like cells with helper function by IL-18.
abstract: Human γδ T cells augment host defense against tumors and infections, and might have a therapeutic potential in immunotherapy. However, mechanism of γδ T cell proliferation is unclear, and therefore it is difficult to prepare sufficient numbers of γδ T cells for clinical immunotherapy. Recently, natural killer (NK)-like CD56(bright)CD11c(+) cells were shown to promote the proliferation of γδ T cells in an IL-18-dependent manner. In this study, we demonstrated that the NK-like CD56(bright)CD11c(+) cells could directly interact with γδ T cells to promote their sustained expansion, while conventional dendritic cells (DCs), IFN-α-induced DCs, plasmacytoid DCs or monocytes did not. We also examined the cellular mechanism underlying the regulation of CD56(bright)CD11c(+) cells. CD14(+) monocytes pre-incubated with IL-2/IL-18 formed intensive interactions with CD56(int)CD11c(+) cells to promote their differentiation to CD56(bright)CD11c(+) cells with helper function. The development of CD56(bright)CD11c(+) cells was suppressed in an IFN-α dependent manner. These results indicate that CD14(+) monocytes pretreated with IL-2/IL-18, but neither DCs nor monocytes, play a determining role on the development and proliferation of CD56(bright)CD11c(+) cells, which in turn modulate the expansion of γδ T cells. CD56(bright)CD11c(+) NK-like cells may be a novel target for immunotherapy utilizing γδ T cells, by overcoming the limitation of γδ T cells proliferation.
authors.affiliation: Laboratory of Tumor Immunology and Cell Therapy, Hyogo College of Medicine, Hyogo, Japan.
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.affiliation: Laboratory of Tumor Immunology and Cell Therapy, Hyogo College of Medicine, Hyogo, Japan ; Department of Pathology, Hyogo College of Medicine, Hyogo, Japan.
authors.forename: Akico
authors.initials: A
authors.lastname: Okuda
authors.affiliation: Laboratory of Tumor Immunology and Cell Therapy, Hyogo College of Medicine, Hyogo, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Laboratory of Tumor Immunology and Cell Therapy, Hyogo College of Medicine, Hyogo, Japan ; Department of Neuropsychiatry, Hyogo College of Medicine, Hyogo, Japan.
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Yamanishi
authors.affiliation: Department of Pathology, Hyogo College of Medicine, Hyogo, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Terada
authors.affiliation: Hirakata General Hospital for Developmental Disorders, Hirakata, Osaka, Japan.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Yamanishi
authors.affiliation: Center for Innovation in Immunoregulative Technology and Therapeutics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Laboratory of Tumor Immunology and Cell Therapy, Hyogo College of Medicine, Hyogo, Japan.
authors.forename: Haruki
authors.initials: H
authors.lastname: Okamura
mesh_terms: D000328:Adult; D039521:CD11c Antigen / Q000378:metabolism*; D019002:CD56 Antigen / Q000378:metabolism*; D002450:Cell Communication / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D020382:Interleukin-18 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D018448:Models, Immunological; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D010641:Phenotype; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*
chemical_list: D039521:CD11c Antigen; D019002:CD56 Antigen; D016898:Interferon-alpha; D020382:Interleukin-18; D018950:Lipopolysaccharide Receptors; D016692:Receptors, Antigen, T-Cell, gamma-delta