Costimulatory molecules and cytotoxic T cells in chronic hepatitis C: Defence mechanisms devoted to host integrity or harmful events favouring liver injury progression? A review

The recruitment of antigen-specific lymphocytes at liver site represents a prominent feature in patients chronically infected with hepatitis C virus (HCV). However, despite the strong and multispecific response, chronic infection leads in a significant number of cases to the development of cirrhosis and hepatocellular carcinoma. The finding that the expression of CD80 structure positively correlates with disease histological worsening points out a role far the costimulatory pathway in the progression of:liver cell injury. On the other hand, the demonstration of CD95 and CD95-ligand positive cells in the context of periportal areas, a pattern which is not strictly associated to HCV tissue distribution, indicates the occurrence of either virus-infected or innocent bystander hepatocyte killing. Nonetheless, the persistence of HCV, in spite of cytotoxic T lymphocyte (CTL) liver recruitment, suggests a possible in-situ imbalance of cytotoxic activities, above all referred to perforin-granzyme-dependent necrosis. Alltogether, these findings outline that several factors might be involved in HCV-driven immunopathogenesis. Therefore, the fully clarification of these mechanisms may offer a suitable therapeutical approach for the improvement of clinical outcome in chronic hepatitis C.