title: Critical role of MHC class I-related chain A and B expression on IFN-alpha-stimulated dendritic cells in NK cell activation: impairment in chronic hepatitis C virus infection.
abstract: Dendritic cells (DCs) augment effector functions of NK cells, but the underlying mechanisms are not fully understood. Here we show in an in vitro coculture system that human monocyte-derived DCs enhance IFN-gamma production, CD69 expression, and K562 cytolytic ability of NK cells when DCs are prestimulated with various maturation stimuli such as IFN-alpha or LPS. Of interest is the finding that NK cell activation mediated by LPS-stimulated DCs was dependent on IL-12 produced in DC/NK coculture, but that IFN-alpha-stimulated DC-mediated activation was not. Alternatively, MHC class I-related chain A and B (MICA/B), ligands for NKG2D activating receptor, were found to be induced on DCs upon IFN-alpha stimulation and to be responsible for the NK activation because mAb-mediated masking of MICA/B as well as inhibition of direct cell-to-cell contact using transwell insert completely abolished DC-dependent NK cell activation by IFN-alpha. Finally, DCs recovered from chronic hepatitis C virus-infected patients showed defects in the induction of MICA/B and impaired ability to activate NK cells in response to IFN-alpha stimulation. These findings suggested that MICA/B induction on DCs may be one of the mechanisms by which IFN-alpha activates NK cells; this impairment might affect IFN-alpha responsiveness in hepatitis C virus infection.
authors.affiliation: Department of Molecular Therapeutics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Masahisa
authors.initials: M
authors.lastname: Jinushi
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Takehara
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kanto
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tatsumi
authors.forename: Veronika
authors.initials: V
authors.lastname: Groh
authors.forename: Thomas
authors.initials: T
authors.lastname: Spies
authors.forename: Takuya
authors.initials: T
authors.lastname: Miyagi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Suzuki
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Norio
authors.initials: N
authors.lastname: Hayashi
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016174:Hepacivirus / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000473:pathology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000502:physiology; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D021122:Protein Subunits / Q000096:biosynthesis / Q000502:physiology; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D016898:Interferon-alpha; D007371:Interferon-gamma; D018664:Interleukin-12; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D021122:Protein Subunits; D000099192:CD69 Antigens; C099187:MHC class I-related chain A; C098080:MICB antigen