Differential CD4(+) and CD8(+) T-cell responsiveness in hepatitis C virus infection

This study was performed to compare the vigor and phenotype of virus-specif ic CD4(+) and CD8(+) T-cell responses in patients with different virologic and clinical outcomes after hepatitis C virus (HCV) infection. The results show that a vigorous and multispecific CD4(+) proliferative T-cell response is maintained indefinitely after recovery from HCV infection whereas it is weak and focused in persistently infected patients. In contrast, the HCV-s pecific CD8(+) T-cell response was quantitatively low in both groups despit e the use of sensitive direct ex vivo intracellular interferon gamma (IFN-g amma) staining. Furthermore, although HCV-specific cytolytic CD8(+) memory T cells were undetectable ex vivo, they were readily expanded from the peri pheral blood of chronically HCV-infected patients but not from recovered su bjects after in vitro stimulation, suggesting that ongoing viremia is requi red to maintain the HCV-specific memory CD8(+) T-cell response, HCV-specifi c CD8(+) T cells displayed a type I cytokine profile characterized by produ ction of IFN-gamma despite persistent HCV viremia. The paradoxical observat ion that HCV-specific CD4(+) T cells survive and CD8(+) T cells are lost af ter viral clearance while the opposite occurs when HCV persists suggests th e existence of differential requirements for the maintenance of CD4(+) and CD8(+) T-cell memory during HCV infection. Furthermore, the relative rarity of circulating CD8(+) effector T cells in chronically infected patients ma y explain the chronic insidious nature of the liver inflammation and also w hy they fail to eliminate the virus.