Vigorous peripheral blood cytotoxic T cell response during the acute phaseof hepatitis C virus infection

After infection by hepatitis C virus (HCV), a minority of patients develop acute symptomatic disease and some of them are able to clear the virus. In this study, we analyzed peripheral blood mononuclear cells from nine patien ts with acute symptomatic disease with respect to their cytotoxic T lymphoc yte (CTL) response using a panel of HCV-derived peptides in a semiquantitat ive secondary in vibro culture system. We could detect early CTL responses in 67% of these patients. The CTL responses were directed against multiple viral epitopes, in particular within the structural (core 2-9, core 35-44, core 131-140, and core 178-187) and nonstructural regions of the virus (NS3 1073-1081, NS3 1406-1415, NS4 1807-1816, NS5 2252-2260, and NS5B 2794-2802 ). We compared the CTL responses displayed by recently and chronically infe cted HLA-A2-positive patients. Virus-specific CTLs were detectable in chron ic carriers but the percentage of positive peptide-specific CTL responses w as significantly higher in recently infected patients (P = 0.002). Follow-u p of recently infected patients during subsequent disease development showe d a significant decrease in the values and proportions of positive peptide- specific CTL responses (P = 0.002 and 0.013, respectively). Patients with l imited viral replication exhibited significantly more vigorous early respon ses (P = 0.024). These data suggest a protective role for the early antivir al CTL response in HCV infection. (C) 2000 Academic Press.