[The immunopathogenesis of hepatitis B]

Knowledge of hepatitis B immunopathogenesis has greatly improved in the last few years thanks to the development of new methods of lymphocyte culture and the introduction of molecular techniques in the study of the cell-mediated antiviral immune responses. Some of the immune mechanisms likely responsible for liver cell injury and viral clearance during hepatitis B have recently been characterized. By using synthetic peptides and high efficiency recombinant expression vectors. HLA class I restricted cytotoxic T cells specifically able to recognize the nucleocapsid antigen of the hepatitis B virus (HBV) have been isolated from the blood of patients with acute self-limited hepatitis B. The observation that this cytotoxic response is lacking or very weak in chronic patients who do not succeed in clearing the virus suggests a major role for cytotoxic T cells in terminating virus infection. Similar behaviour is shown by HLA class II restricted CD4+ T cells which express much stronger levels of response to HBV nucleocapsid antigens in acute than in chronic HBV infection. Whether these defective responses in chronic patients are due to an actual lesion of the host's immune system or to viral mutations affecting immune surveillance and thereby allowing virus escape, still remain open issues. A definitive answer to these questions will, we hope, provide the appropriate tools to devise effective immune therapies against chronic HBV infection.