In particular, HCV-specific CD8 T cells have been reported to express increased levels of PD-1 and an exhausted phenotype (weak proliferation, IFN-γ production, and cytotoxicity) [37]–[41].Although depletion studies in the chimpanzee model are consistent with a role of CD8+T cells as primary effector of protective immunity [42], studies in natural HCV infection were unable to find clear correlations between HCV-specific CD8+ T cell responsiveness and outcome of infection [37]–[41], [43], [44]. The gene discussed is IFNG; the disease is infection.