Decreased frequency of HCV core-specific peripheral blood mononuclear cells with type 1 cytokine secretion in chronic hepatitis C

Background/Aim: Since the outcome of hepatitis C infection appears to be correlated with the immune response to the HCV core protein, the aim of this study was to investigate the T cell response to hepatitis C virus core and core-derived antigens. Methods: As this response may be regulated importantly by differential secretion of cytokines, we determined the number of peripheral blood mononuclear cells (PBMC) that secreted IL-2, IL-4, IL-10, and IFN-γ in response to a recombinant HCV core protein and a panel of 19 core-derived peptides, using the ELI-Spot-technique. Two groups of patients were studied: group A: 11 patients with previously self-limited HCV infection; group B: 12 patients with chronic hepatitis C. Results: In group B significantly less IFN-γ spot forming cells (SFC) could be detected, both after stimulation with the core protein (0.083±0.083 SFC vs. 1.3±0.4 SFC/105 PBMC; p=0.005) and with the core-derived peptides (1.3±0.5 vs. 4.4±1.1 SFC SFC/105 PBMC; p=0.007). By analyzing the cytokine response to each single peptide, we found IFN-γ responses to peptides aa 39–63 and aa 148–172 in group A but not in group B (p<0.03). In group B also, fewer IL-2 secreting cells were found after peptide stimulation (p=0.04). Whereas subjects of group B showed IL-10-specific responses to HCV peptides more frequently than patients with self-limiting hepatitis C (p=0.03), the number of IL-4-producing cells was not different between the two groups. Conclusions: The data suggest that patients with persistent viremia and chronic liver disease (group B) have less PBMC showing type 1 cytokine (IL-2, IFN-γ) responses to HCV core protein than patients with self-limited HCV infection (group A).