Significant effect of hepatitis C virus specific CTLs on viral clearance in patients with type C chronic hepatitis treated with antiviral agents

Aim: To evaluate the correlation between hepatitis C virus (HCV) specific cytotoxic T lymphocytes (CTLs) and viral clearance in antiviral treated patients, we examined the number and function of HCV epitope-specific CTLs and the viral load in 12 HLA-A2-positive patients with chronic hepatitis C, after undergoing interferon therapy. Methods: Peripheral blood mononuclear cells (PBMC) were analyzed on days 0, 3, 7, 14 and 28 of undergoing antiviral therapies. To investigate the quantity of the antigen specific CTLs, CD8-positive T cells were isolated using microbeads and were stained for HLA-A*0201 tetramers. To investigate the function of CTLs, PBMC were stimulated with the same synthetic epitope peptides and analyzed to determine their interferon (IFN)-gamma expression. Results: In seven patients, HCV-RNA became undetectable 4 weeks after antiviral therapies (EVR), but five patients were non-responders (NR). In peptide NS3 1406 on day 3 and day 7 of therapy and in NS3 1073 on day 3 of therapy, the level of IFN-gamma expression on CD8+ T cells was significantly higher in the EVR group than in the NR group. In other peptides, the number of and cytokine production from the CTLs in the EVR group were also higher than in the NR group, but not significantly. Conclusion: After antiviral therapy, analysis of the number and function of antigen-specific CTLs in the early phase was thus found to be useful for predicting viral clearance in chronic hepatitis C patients.