title: CD154, a marker of antigen-specific stimulation of CD4 T cells, is associated with response to treatment in patients with chronic HCV infection.
abstract: CD4 T-cell function is crucial for the eradication of HCV, and insufficient function is observed in chronic carriers. The monitoring of T-cell responses is complicated by the scarcity of antigen-specific T cells and the relative inefficiency of virus-specific T cells to produce effector cytokines. CD154 is a marker of activation expressed on T cells induced through their T-cell receptor. We analysed CD4 T-cell responses in 72 patients with chronic or resolved HCV infection (23 treatment naïve, 49 treatment experienced, including 16 who had achieved a sustained response). In an additional prospective protocol, 20 of the chronically infected patients were analysed before and after 8-12 weeks of combination therapy with peg-interferon-α and ribavirin. T-cell responses were measured by detecting the expression of CD154 and Th1 cytokines after stimulation with recombinant HCV proteins and were correlated with pretreatment status and outcome of therapy. Broader T-cell responses were observed in treatment naïve than in experienced patients, while the outcome of a preceding therapy regimen did not influence T-cell responses. In the prospective cohort, an on-treatment increase in CD154+ cytokine- T-cell activity was associated with response to treatment, while a decrease was observed in nonresponders. Stronger antigen-independent activity of CD154+ cytokine+ T cells was observed in responders than in nonresponders. Our data indicate that CD154 as a marker of activation of CD4 T cells is a suitable tool for the analysis of T-cell responses in patients with HCV infection.
authors.affiliation: Medizinische Klinik m.S. Hepatologie und Gastroenterologie, Charité Universitätsmedizin Berlin, CVK, Berlin Hepatologische Schwerpunktpraxis, Berlin, Germany.
authors.forename: J F
authors.initials: JF
authors.lastname: Möller
authors.forename: B
authors.initials: B
authors.lastname: Möller
authors.forename: B
authors.initials: B
authors.lastname: Wiedenmann
authors.forename: T
authors.initials: T
authors.lastname: Berg
authors.forename: E
authors.initials: E
authors.lastname: Schott
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D023201:CD40 Ligand / Q000096:biosynthesis*; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D016898:Interferon-alpha; D011994:Recombinant Proteins; D023201:CD40 Ligand; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a