Subversion of effector CD8+ T cell differentiation in acute hepatitis C virus infection: exploring the immunological mechanisms.

Hallmark of acute hepatitis C virus (HCV) infection is a severe virus-specific effector CD8(+) T cell dysfunction that seems to be a critical factor in preventing the resolution of infection and in favoring the onset of chronic liver immunopathology. We suggest that this dysfunction is critical in the establishment of HCV persistence, unless it is compensated by multispecific responses, as found in individuals resolving infection. Analyses on purified populations indicate that central memory HCV-specific CCR7(+)/CD8(+) T cells efficiently proliferate and differentiate in vitro, although the large population of memory effector CCR7(-) cells found in the peripheral blood of acutely infected patients display poor effector functions ex vivo (semi-effectors).