Liver tissue expression of CD80 and CD95 antigens in chronic hepatitis C: relationship with biological and histological disease activities.

The well known discrepancy between cytotoxic T lymphocyte (CTL) infiltration in the liver and disease biological activity, as assessed by alanine aminotransferase (ALT) levels, during the course of chronic hepatitis C virus (HCV) infection, suggests the possible failure of cytotoxic mechanisms devoted to virus clearance. To further investigate the biological events involved in CTL-mediated lysis, i.e. B7/CD28 costimulatory and Fas/Fas-ligand pathways, the CD80 and CD95 antigen expression in liver tissue specimens from chronically HCV-infected patients was evaluated. The results were analysed in relation to serum ALT values and the histological activity (HAI) of liver disease. The data provide evidence for a strong and comparable hepatocyte CD80 and C95 structure expression in chronically HCV-infected livers. CD80- and CD95-carrying liver cells were more frequently distributed at the periportal region of the hepatic lobule, above all near piecemeal necrosis areas, among infiltrating CTL. On the other hand, a negative correlation was found between liver tissue expression of both antigens and serum ALT activity. The relationship with HAI was not statistically significant. The results imply that HCV infection triggers CD80 and CD95 molecule expression on hepatocytes. Further studies are required to clarify the relevance of such a finding in the context of virus-host interactions.

CD45RA and CD45RO isoform expression on intrahepatic T-lymphocytes in chronic hepatitis C.

A liver tissue recruitment of antigen-specific cytotoxic cells has been reported in chronic hepatitis C virus (HCV) infection, but whether they really play a role in viral clearance is still a matter of investigation. To further evaluate T-cell involvement in HCV-induced hepatic disease, the authors analysed, in a cohort of chronic hepatitis C patients, the intrahepatic T-cell expression of CD45 isoforms by using specific monoclonal antibodies. Within hepatic specimens, CD45RA+ (naive) cell frequency at the portal tract level was significantly higher than that exhibited at lobular level. At the same time, a large number of CD45RO+ (memory) cells was found at periportal sites in comparison with the lobular counterpart. The evaluation of CD45RA and CD45RO isoform topographical distribution in relation to CD4+ and CD8+ lymphocytes, as determined on serial sections, showed that CD45RA antigen expression was predominantly coexpressed with CD4+ lymphocytes at the portal tract level, and the CD45RO phenotype with CD8 structure at the lobular and periportal sites. The levels of CD45 isoforms did not show any correlation with biological and/or histological disease activities. The results suggest that a liver recruitment of both naive and memory cells occurs during chronic HCV infection, even if their functional role needs to be further clarified.