Cell-mediated immune responses to HCV antigens may play a role in the pathogenes is of chronic liver disease, viral persistence, and treatment outcome in patients with HCV infection. Observations suggest that CD8 + T cells may be critical for successful HCV clearance. Lцhr et al (University of Mainz, Germany) analyzed the ratios of CD4+ and CD8+ T cell populations and the proliferative helper T cell responses to a panel of recombinant HCV antigens in the clinical course of 42 chronic HCV carriers followed for 6 to 18 months. Of these, 31 received 3-12 months of IFN alfa 4.5 MU TIW. Six patients attained a complete response, 6 were trainsient responders, and 19 were nonresponders.
In this study, CD4/CD8 ratios varied in chronic HCV carriers and did not correlate with response to IFN alfa therapy. HCV structural and non-structural antigens were immunogenic in patients with chronic HCV infection. NS3/NS4-specific T helper cell responses were associated with HCV clearance, while core and NS5-antigen specific T helper cells appeared to promote viral persistence. In a second study, these investigators also reported cytotoxic T-cell lymphocyte responses in 9 of 15 HLA-A2-chronic HCV carriers but 0 of 3 HLA-A2- patients and 0 of 3 HLA-A2 + healthy controls.
In patients receiving IFN alfa, an initial increase in cytotoxic T-cell lymphocyte precursors occurred simultaneously with viral clearance in 3 patients who had a complete response to therapy; this was not observed in 3 patients who did not respond to IFN therapy. In another study reported by Lasarte et al (University of Navarro, Pamplona, Spain), patients who had a sustained response to IFN treatment showed 5-6 times higher frequencies of T helper cells against HCV core protein compared with untreated or nonresponding patients (P
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