Quantitative and functional differences in CD8(+) lymphocyte responses in resolved acute and chronic hepatitis C virus infection.
J VIRAL HEPATITIS
18 - 28.
CD8(+) lymphocyte responses are important in the clearance of viral infections. In chronic infections they may contribute to pathogenesis, To investigate the role of CD8(+) T lymphocyte responses in viral clearance and chronic hepatitis C we have compared hepatitis C virus (HCV) specific cytotoxicity and interferon-gamma (IFN-gamma) production in patients with resolved-acute. and chronic HCV infection. CD8(+) T cell responses to a panel of 13 HCV T cell peptide epitopes were studied using Elispot assays of IFN-gamma production and chromium release cytotoxicity assays, Responses of seven patients with resolved acute HCV infection were compared with those of 14 chronically infected patients. HCV-specific cytotoxicity differentiated the two populations of patients. The majority (71%) of patients with resolved acute infection tested positive to 42% of relevant peptides compared with the minority (28%) of patients with chronic hepatitis C (P=0.03) who responded to only 8% of relevant peptides (P=0.0009). In contrast, HCV-specific IFN-gamma production was detected in 86% of patients with either resolved or chronic infection in response to 42% and 35%, respectively, of relevant peptides tested (not significant), In patients with chronic infection the magnitude of the HCV-specific IFN-gamma production was inversely correlated to viral load (R-2=0.52: P=0.042). Failure to clear HCV infection may be attributable to the presence of noncytolytic IFN-gamma producing CD8(+) T lymphocytes fit chronically infected patients. However these CD8(+) T cells may play a beneficial role in contributing to the control of viral load in chronic hepatitis C.
|Title:||Quantitative and functional differences in CD8(+) lymphocyte responses in resolved acute and chronic hepatitis C virus infection|
|Keywords:||cytotoxic T cells, HCV, interferon-gamma, CYTOTOXIC T-LYMPHOCYTES, IMMUNE-RESPONSES, B VIRUS, PERIPHERAL-BLOOD, CELLS, ASSOCIATION, EPITOPE, PATHOGENESIS, PERSISTENCE, EXPRESSION|
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