Analysis of hepatitis C virus-specific CD8+ T-cells with HLA-A*24 tetramers during phlebotomy and interferon therapy for chronic hepatitis C.

Hepatitis C virus (HCV)-specific, HLA class I-restricted, CD8-positive (CD8+) T lymphocytes are thought to contribute to viral clearance as well as liver disease in chronic hepatitis C. For the patients who do not respond to interferon (IFN) therapy, phlebotomy can be used as a tool to reduce inflammation and lower transaminase levels; however, the immunological aspects have not been clearly defined. In this study, we evaluated the HCV-specific CD8+ T-cell responses during phlebotomy and IFN therapy using HLA-A*24 tetramers in 6 Japanese patients with chronic hepatitis C. During phlebotomy, 4 of the 6 cases achieved a biochemical response, but there was no clear correlation between its efficacy and HCV viral loads or changes in frequencies or activation status of tetramer-positive T-cells. In contrast, the frequencies of tetramer-positive cells and the proportions of T-cells expressing activation marker HLA-DR were higher in sustained viral responders than in transient responders to IFN therapy. Furthermore, expression of the activation marker was enhanced in the initial period of IFN therapy. The results suggest that the immunological aspects of phlebotomy obviously differ from those of IFN therapy and these differences may provide clues as to a therapeutic strategy of their combination for patients who do not respond to IFN monotherapy.