title: Circulating Valpha24+Vbeta11+ NKT cell numbers and dendritic cell CD1d expression in hepatitis C virus infected patients.
abstract: CD1d-restricted natural killer T (NKT) cells are involved in the regulation of various immune responses, and have been shown to inhibit viral replication in animal hepatitis models when activated by the glycolipid alpha-galactosylceramide (alpha-GalCer, KRN7000). Previous studies have indicated that alpha-GalCer-induced activation of the immune system requires both CD1d expression by antigen-presenting cells as well as (normal) numbers of NKT cells. Discrepancies exist over circulating numbers of human invariant Valpha24+Vbeta11+ NKT cells during hepatitis C virus (HCV) infection. Here, by cross-sectional analysis and longitudinal analysis of patients undergoing effective combination antiviral therapy, we demonstrate that circulating Valpha24+Vbeta11+ NKT cell numbers are not decreased during active HCV infection. Importantly, as we also show that CD1d is expressed at comparable levels by peripheral blood monocytes and CD1c+ myeloid dendritic cells (DC) of healthy individuals and HCV-infected patients, these data indicate that all ingredients for evaluating the antiviral effects of the Valpha24+Vbeta11+ NKT cell ligand alpha-GalCer in HCV-infected patients are present.
authors.affiliation: Department of Internal Medicine, Vrije Universiteit Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. jj.vandervliet@vumc.nl
authors.forename: Hans J J
authors.initials: HJ
authors.lastname: van der Vliet
authors.forename: Johan W
authors.initials: JW
authors.lastname: Molling
authors.forename: B Mary E
authors.initials: BM
authors.lastname: von Blomberg
authors.forename: Wendy
authors.initials: W
authors.lastname: Kölgen
authors.forename: Anita G
authors.initials: AG
authors.lastname: Stam
authors.forename: Tanja D
authors.initials: TD
authors.lastname: de Gruijl
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Mulder
authors.forename: Harry L A
authors.initials: HL
authors.lastname: Janssen
authors.forename: Nobusuke
authors.initials: N
authors.lastname: Nishi
authors.forename: Alfons J M
authors.initials: AJ
authors.lastname: van den Eertwegh
authors.forename: Rik J
authors.initials: RJ
authors.lastname: Scheper
authors.forename: Carin J M
authors.initials: CJ
authors.lastname: van Nieuwkerk
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018949:Antigens, CD1 / Q000096:biosynthesis / Q000276:immunology*; D055610:Antigens, CD1d; D000998:Antiviral Agents / Q000627:therapeutic use; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D005260:Female; D005434:Flow Cytometry; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D006801:Humans; D016130:Immunophenotyping; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000276:immunology* / Q000821:virology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000821:virology
chemical_list: D018949:Antigens, CD1; D055610:Antigens, CD1d; D000998:Antiviral Agents; C526877:CD1D protein, human; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b