COSTIMULATORY MOLECULES AND CYTOTOXIC T-CELLS IN CHRONIC HEPATITIS-C - DEFENSE-MECHANISMS DEVOTED TO HOST INTEGRITY OR HARMFUL EVENTS FAVORING LIVER-INJURY PROGRESSION - A REVIEW

The recruitment of antigen-specific lymphocytes at liver site represen ts 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 deve lopment of cirrhosis and hepatocellular carcinoma. The finding that th e expression of CD80 structure positively correlates with disease hist ological worsening points out a role far the costimulatory pathway in the progression of:liver cell injury. On the other hand, the demonstra tion of CD95 and CD95-ligand positive cells in the context of periport al areas, a pattern which is not strictly associated to HCV tissue dis tribution, indicates the occurrence of either virus-infected or innoce nt 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 referre d to perforin-granzyme-dependent necrosis. Alltogether, these findings outline that several factors might be involved in HCV-driven immunopa thogenesis. Therefore, the fully clarification of these mechanisms may offer a suitable therapeutical approach for the improvement of clinic al outcome in chronic hepatitis C.