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 co rrelated 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 secr etion of cytokines, we determined the number of peripheral blood mononuclea r cells (PBMC) that secreted IL-2, IL-4, IL-10, and IFN-gamma in response t o a recombinant HCV fore protein and a panel of 19 core-derived peptides, u sing the ELI-Spot-technique, Two groups of patients were studied: group A: 11 patients with previously self-limited HCV infection; group B: 12 patient s with chronic hepatitis C. Results: In group B significantly less IFN-gamma, spot forming cells (SFC) could be detected, both after stimulation with the core protein (0.0830+/-0 .083 SFC vs, 1.3+/-0.4 SFC/10(5) PBMC; p=0.005) and with the core-derived p eptides (1.3+/-0.5 vs. 4.4+/-1.1 SFC SFC/10(-5) PBMC; p=0.007). By analyzin g the cytokine response to each single peptide, we found IFN-gamma response s 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 sti mulation (p=0.04), Whereas subjects of group B showed IL-10-specific respon ses to HCV peptides more frequently than patients with self-limiting hepati tis C (p=0.03), the number of IL-4-producing cells was not different betwee n the two groups. Conclusions: The data suggest that patients with persistent viremia and chr onic liver disease (group B) have less PBMC showing type 1 cytokine (IL-2, IFN-gamma) responses to HCV core protein than patients with self-limited HC V infection (group A).