HLA-A2-RESTRICTED CYTOTOXIC T LYMPHOCYTE ACTIVITY DURING INTERFERON BETA THERAPY IN PATIENTS WITH CHRONIC HEPATITIS C

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Background and Aims: Hepatitis C virus (HCV)-specific cytotoxic T lymphocytes (CTL) may contribute to viral clearance and liver cell injury in patients with chronic hepatitis C. In the present study, we attempted to determine the serial HCV-specific CTL activity during interferon-beta (IFN-β) therapy in patients with chronic hepatitis C and whether there is any relationship between the CTL response and clinical response to IFN-β therapy.
Methods: Eight HLA-A2-positive patients with chronic hepatitis C were treated initially with 6 million U/ml of IFN-β every day for 8 weeks and then 3 times weekly for the subsequent 16 weeks. Peripheral blood mononuclear cells (PBMC) were collected before the start, 4 weeks after the start, and after the end of IFN treatment and were stimulated with 2 peptides corresponding to core sequences, which were previously reported to have an HLA-A2 restricted-CTL epitopes. Cytolytic activity was determined by a standard ⁵¹Cr-release assay using allogenic HLA-matched EBV-transformed B lymphoblastoid cell lines (B-LCL).
Results: HCV-specific CTL responses were detected in 2 of the 8 patients before treatment with IFN-β. One of 2 patients was not observed HCV-specific CTL responses after 4 weeks of IFN-β treatment, however these two patients showed CTL responses at the end of IFN-β treatment, and finally HCV-RNA was negative. In addition, HCV-specific CTL responses were observed in 4 patients after 4 weeks of IFN-β treatment. Three of these 4 patients showed CTL responses only at 4 weeks after IFN-β treatment. However, there were no differences between clinical parameters or between IFN efficacy in HCV-specific CTL response- positive (n=4) and -negative (n=4) patients at 4 weeks after the start of IFN-β treatment.
Conclusions: These findings suggest that there are few relations between peripheral HCV-specific CTL response and clinical response to IFN therapy in patients with chronic hepatitis C, although IFN enhances the host immune response against HCV synergistically with antiviral activities.