Aim: Hepatitis C virus (HCV)-specific cytotoxic T lymphocytes (CTLs) play critical roles in elimination of the HCV-infected hepatocytes. However, the mechanism of HCV elimination by pegylated interferon-α (peg-IFNα) plus ribavirin is not fully understood. We examined HCV-specific CTL responses during this combination therapy.
Methods: CD8+ T cells were isolated from 16 HCV infected patients treated by this combination therapy and were subjected to IFN-γ enzyme-linked immunospot (ELISPOT) assay.
Results: The numbers of IFN-γ spots against HCV Core or NS3 protein-derived peptides in HCV patients before treatment were similar to those in healthy donors, and those in HCV patients significantly increased 4 weeks after the initiation of combination therapy. All HCV Core or NS3 proteins-derived peptides specific CD8+ T cells responses in pre-treated patients were not associated with ALT levels and HCV viral loads of HCV patients before treatment. And those in pre-treated patients were similar between sustained virologic responder (SVR) patients and non-SVR patients. Significant increase of HCV Core or NS3 proteins-derived peptides specific CD8+ T cells responses between before and 4 weeks after this combination therapy were observed in SVR patients, but not in non-SVR patients.
Conclusions: These results demonstrated that significant increase of HCV-specific CD8+ T cells at 4 weeks after the initiation of IFN treatment might be associated with the elimination of HCV. Our findings suggest that the reactivity against HCV Core and NS3 proteins-derived peptides might be useful in predicting the clinical outcome of the combination therapy of peg-IFNα and ribavirin.
© 2010 The Japan Society of Hepatology.