title: Maintenance of Th1 hepatitis C virus (HCV)-specific responses in individuals with acute HCV who achieve sustained virological clearance after treatment.
abstract: OBJECTIVE
  T-cell responses against hepatitis C are believed to be critical in achieving both natural and treatment-induced clearance. However, rapid clearance of antigen with early treatment of primary infection may result in reduced or poorly sustained cellular immunity. This study longitudinally examined Th1 and Th2 hepatitis C virus (HCV)-specific cytokine production and T-cell effector function from subjects enrolled in the Australian Trial in Acute Hepatitis C comparing three groups: treatment-induced clearance (sustained virological response [SVR]), treatment non-response, and untreated spontaneous clearance.
  
  
  METHODS
  HCV-specific T-cell responses were characterized by HCV peptide ELISpot, in vitro cytokine production, and T-cell flow cytometry assays.
  
  
  RESULTS
  Treated subjects with a sustained virological response (SVR) displayed a better maintenance of HCV-specific Th1 responses compared to treatment non-responders (higher interferon [IFN]-γ and interleukin (IL)-2 magnitude at week 24, broader IFN-γ responses at weeks 24 and 48, P < 0.05) and significantly increased IFN-γ responses between screening and week 48 (magnitude P = 0.026, breadth P = 0.009). Treatment-induced viral clearance was also associated with a trend toward decreased IL-10 responses (screening to week 48, P = 0.070), higher expression of CD45RO (P = 0.042) and CD38 (P = 0.088) on CD4+ T cells, and higher IFN-γR expression (CD56+ IFN-γR+ P = 0.033) compared to treatment non-responders. Untreated subjects with viral clearance also displayed high magnitude and broad HCV-specific IFN-γ and IL-2 responses early in infection; however, IFN-γ responses were not as well maintained compared to treated subjects with a SVR (week 48 magnitude, breadth P = 0.064).
  
  
  CONCLUSIONS
  Treatment-induced viral clearance of recent HCV infection is associated with maintenance of HCV-specific Th1 responses.
authors.affiliation: Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia; Department of Immunology, Monash University, Melbourne, Victoria, Australia.
authors.forename: Jacqueline K
authors.initials: JK
authors.lastname: Flynn
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dore
authors.forename: Margaret
authors.initials: M
authors.lastname: Hellard
authors.forename: Barbara
authors.initials: B
authors.lastname: Yeung
authors.forename: William D
authors.initials: WD
authors.lastname: Rawlinson
authors.forename: Peter A
authors.initials: PA
authors.lastname: White
authors.forename: John M
authors.initials: JM
authors.lastname: Kaldor
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Lloyd
authors.forename: Rosemary A
authors.initials: RA
authors.lastname: Ffrench
mesh_terms: D000208:Acute Disease; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D002478:Cells, Cultured; D005260:Female; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000188:drug therapy / Q000276:immunology* / Q000821:virology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology; D008137:Longitudinal Studies; D008297:Male; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D000998:Antiviral Agents; D007376:Interleukin-2; D007371:Interferon-gamma
keywords: PEG-IFN-α; T cells; acute hepatitis C; immune response; injecting drug users