title: Intrahepatic CD8+ T-lymphocyte response is important for therapy-induced viral clearance in chronic hepatitis B infection.
abstract: OBJECTIVE
  To determine which immune cells contribute to HBV-clearance during antiviral therapy, we performed a longitudinal analysis of intrahepatic immune cells during interferon-alpha therapy of chronic HBV-patients using the FNAB technique.
  
  
  METHODS
  Twenty chronic HBeAg+-patients were treated with pegylated alpha-interferon combined with lamivudine or placebo for 52 weeks. FNAB and blood specimens were obtained at week 0, 2, 8 and 52. CD4+- and CD8+ T-lymphocytes, CD56+ cells, IFNgamma and granzyme B (GrB) were immunocytochemically quantified.
  
  
  RESULTS
  The relative numbers of CD56+ cells and CD8+ T-lymphocytes were significantly higher in FNAB compared to blood at all time-points. Responders (n=9) exhibited significant increases in intrahepatic CD8+ and CD8+GrB+ lymphocytes, a small elevation in CD8+IFNgamma+ T-lymphocytes, no change in CD4+ T-lymphocytes, and a decrease in intrahepatic CD56+ cells during the first weeks of therapy. In non-responders (n=11) no significant changes in CD4+- and CD8+ T-lymphocytes and an increase in intrahepatic and CD56+ cells were observed during therapy.
  
  
  CONCLUSIONS
  The intrahepatic CD8+ T-lymphocyte, but not the CD4+ T-lymphocyte or NK/NKT-cell response, is important for HBV clearance during interferon-alpha therapy, and the antiviral effect may be mediated by both cytolytic and non-cytolytic mechanisms.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center Rotterdam, Room L-455, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands.
authors.forename: Thjon J
authors.initials: TJ
authors.lastname: Tang
authors.forename: Jaap
authors.initials: J
authors.lastname: Kwekkeboom
authors.forename: Shanta
authors.initials: S
authors.lastname: Mancham
authors.forename: Rekha S
authors.initials: RS
authors.lastname: Binda
authors.forename: Robert A
authors.initials: RA
authors.lastname: de Man
authors.forename: Solko W
authors.initials: SW
authors.lastname: Schalm
authors.forename: Johannes G
authors.initials: JG
authors.lastname: Kusters
authors.forename: Harry L A
authors.initials: HL
authors.lastname: Janssen
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D019002:CD56 Antigen / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D002452:Cell Count; D004359:Drug Therapy, Combination; D005260:Female; D053804:Granzymes; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy* / Q000473:pathology* / Q000821:virology; D006801:Humans; D007150:Immunohistochemistry; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000378:metabolism; D019259:Lamivudine / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008137:Longitudinal Studies; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D012697:Serine Endopeptidases / Q000378:metabolism; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D019002:CD56 Antigen; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D011092:Polyethylene Glycols; D007371:Interferon-gamma; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases; C417083:peginterferon alfa-2b