CD8(+) T lymphocyte responses are induced during acute hepatitis C virus infection but are not sustained

Cellular immune responses are likely to play a key role in determining the clinical outcome in acute infection with hepatitis C virus (HCV), but the d ynamics of such responses and their relationship to viral clearance are poo rly understood. In a previous study we have shown highly activated, multisp ecific cytotoxic T lymphocyte responses arising early and persisting in an individual who subsequently cleared the virus. In this study the HCV-specif ic CD8(+) lymphocytes response has been similarly analyzed, using peptide-H LA class I tetramers, in a further nine individuals with documented acute H CV infection, six of whom failed to clear the virus. Significant population s of virus-specific CD8(+) lymphocytes were detected at the peak of acute h epatic illness (maximally 3.5 % of CD8(+) lymphocytes). Frequencies were co mmonly lower than those seen previously and were generally not sustained. E arly HCV-specific CD8(+) lymphocytes showed an activated phenotype in all p atients (CD38(+) and HLA class II+), but this activation was short-lived. F ailure to sustain sufficient numbers of activated virus-specific CD8(+) lym phocytes may contribute to persistence of HCV.