Hepatitis C virus-specific cytolytic T cell responses after antiviral therapy.
Antigen-specific T cells are likely to provide a critical defense against hepatitis C virus (HCV) infection. However, their detection in blood is uncommon except in persons who undergo spontaneous recovery after acute HCV infection. We postulated that virological responses after antiviral interferon-alpha therapy may be associated with enhanced cytolytic T cell immunity. Peripheral blood memory CTL responses were quantified using short term limiting dilution culture, with cytolytic function detected by standard chromium release assay. In this cross-sectional study, 5 of 11 interferon-alpha or interferon-alpha plus ribavirin-treated subjects exhibited cytolytic T cell responses after therapy completion; 4 of these 5 subjects were HCV RNA negative at the time of assay. In contrast, only 1 of 9 untreated chronically viremic subjects had detectable HCV-specific cytolytic T cell responses. Although the requisite factors necessary to achieve sustained virologic response after therapy remain largely undefined, the findings presented here suggest that antiviral therapy-induced virological clearance may be associated with the induction, expansion, and/or recirculation of HCV antigen-specific cytolytic T cells, and may play a role in the maintenance of a nonviremic state.
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D002455:Cell Division; D002478:Cells, Cultured; D003430:Cross-Sectional Studies; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007370:Interferon Type I / Q000627:therapeutic use*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D013045:Species Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014766:Viremia
D000998:Antiviral Agents; D007370:Interferon Type I; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin