Concomitant augmentation of type 1 CD4⁺ and CD8⁺ T-cell responses during successful interferon-α and ribavirin treatment for chronic hepatitis C virus infection

The combined interferon-α (IFN-α) and ribavirin (IFN-α/ribavirin) therapy for chronic hepatitis C virus (HCV) infection results in sustained viral eradication in 31%-64% of the patients. Previous studies have strongly suggested that HCV-specific T-cell responses maybe modulated during this therapy. The objective of this study was to further define the effect of IFN-α/ ribavirin therapy on type 1 and type 2 HCV-specific CD4⁺ and CD8⁺ T-cell responses during IFN-α/ribavirin therapy. Toward this, serial CD8⁺ T-cell responses to HCV-derived epitopes and CD4⁺ T-cell responses to the HCV core antigen were analyzed in four patients before (baseline), during (at 24 weeks), and at the end (at 48 weeks) of IFN-α/ribavirin therapy. Therapy-induced viral clearance in three patients was associated with a significant augmentation of HCV-specific type 1 CD4⁺ and CD8⁺ T-cell responses. In contrast, in a patient who did not respond to therapy, a significant HCV-specific CD4⁺ Th2 cell reactivity was observed accompanied by a lack of augmentation of the HCV-specific CD8⁺ T-cell reactivity. These results indicate that enhancement of HCV-specific CD4⁺ and CD8⁺ T-cell responses is an important factor in determining the response to the IFN-α/ribavirin therapy and the outcome of the HCV infection.