Circulating Valpha24+Vbeta11+ NKT cell numbers and dendritic cell CD1d expression in hepatitis C virus infected patients.
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.
van der Vliet
Hans J J
HJ
Department of Internal Medicine, Vrije Universiteit Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. jj.vandervliet@vumc.nl
Molling
Johan W
JW
von Blomberg
B Mary E
BM
Kölgen
Wendy
W
Stam
Anita G
AG
de Gruijl
Tanja D
TD
Mulder
Chris J
CJ
Janssen
Harry L A
HL
Nishi
Nobusuke
N
van den Eertwegh
Alfons J M
AJ
Scheper
Rik J
RJ
van Nieuwkerk
Carin J M
CJ
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
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