title: Impaired allostimulatory capacity of peripheral blood dendritic cells recovered from hepatitis C virus-infected individuals.
abstract: In hepatitis C virus (HCV) infection, Th responses are implicated in the pathogenesis of liver disease. The dendritic cell (DC) is the most potent activator of CD4 T cells for supporting Th1 differentiation. To clarify the roles of DC of HCV-infected individuals in the development of CD4 T cell responses, we generated peripheral DC with GM-CSF and IL-4 from 24 chronic hepatitis C patients and 14 healthy donors. We then compared their potentials for stimulating allogeneic CD4 T cells, autologous CD4 T cells against influenza A or HCV core Ags, and cytokine production. The DC from the patients (HCV-DC) expressed lower degrees of CD86 than DC from the donors (N-DC), whereas no difference was found in the HLA molecules and other costimulators. HCV-DC stimulated allogeneic T cells less than N-DC; however, influenza A- or core-pulsed HCV-DC retained the potentials for autologous T cell proliferation. In allogeneic DC/T cell cultures, the IFN-gamma levels with HCV-DC were lower than those with N-DC, which may be related to the low expressions of IL-12 p35 and p40 transcripts in HCV-DC. The stimulation with LPS disclosed that HCV-DC is less potent in IL-12 p70 production than N-DC. In the autologous cultures, the pulsing of the Ags to HCV-DC increased the IL-12 p40 and IFN-gamma production and up-regulated the transcription of both IL-12 subunits. Exogenous IL-2 or IL-12 restored the low allogeneic T cell proliferation with HCV-DC in a dose-dependent manner. Therefore, low expression of CD86 and/or IL-12 is crucially involved in the low allostimulatory capacity of HCV-DC. Low IL-12 and low IFN-gamma milieu with HCV-DC on encounters with alloantigens may impede Th1 polarization.
authors.affiliation: First Department of Medicine and Department of General Medicine, Osaka University Medical School, Suita, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kanto
authors.forename: N
authors.initials: N
authors.lastname: Hayashi
authors.forename: T
authors.initials: T
authors.lastname: Takehara
authors.forename: T
authors.initials: T
authors.lastname: Tatsumi
authors.forename: N
authors.initials: N
authors.lastname: Kuzushita
authors.forename: A
authors.initials: A
authors.lastname: Ito
authors.forename: Y
authors.initials: Y
authors.lastname: Sasaki
authors.forename: A
authors.initials: A
authors.lastname: Kasahara
authors.forename: M
authors.initials: M
authors.lastname: Hori
mesh_terms: D000328:Adult; D017951:Antigen Presentation; D000955:Antigens, T-Independent / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000145:classification / Q000276:immunology* / Q000378:metabolism; D003911:Dextrans / Q000032:analysis / Q000378:metabolism; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000378:metabolism; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000097:blood / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D014158:Transcription, Genetic / Q000276:immunology
chemical_list: D000955:Antigens, T-Independent; D003911:Dextrans; D007376:Interleukin-2; D008070:Lipopolysaccharides; C015219:fluorescein isothiocyanate dextran; D018664:Interleukin-12; D007371:Interferon-gamma; D016650:Fluorescein-5-isothiocyanate