Soluble HLA class I antigens in chronic hepatitis C: A disease-associated manifestation or molecules modulating immunoresponsiveness?

The occurrence of high levels of soluble human leukocyte class I antigens ( sHLA-I) represents an usual finding during the-course of:different clinical conditions, such as viral infections and autoimmune disorders. On the othe r hand, the well known property of sHLA-I to modulate T cell responsiveness could be taken as an advantage to improve long-term allograft acceptance. Recent data have pointed out that subjects with chronic hepatitis C virus ( HCV) infection exhibit high amounts of sHLA-I, a pattern which has also bee n used for monitoring host responsiveness to interferon alpha (IFN-alpha) t herapy. However, the lack-of correlation between lymphocyte infiltration at liver site and disease biological activity suggests a potential role for s HLA-I in:T cell dysfunction during chronic hepatitis C, sHLA-I antigens may , in fact, either interact with T cell receptor delivering an inhibitory si gnal or trigger cytotoxic T lymphocyte apoptosis by inducing CD95 ligand ex pression. Both events seem to favour HCV replication and liver tissue damag e progression. Alltogether, these findings indicate that, besides viral variant generation and HCV core-mediated immunosuppression, sHLA-I may contribute to the imba lance of immunoresponsiveness during chronic HCV infection.