IMMUNE-RESPONSES IN HEPATITIS-C VIRUS-INFECTION

Infection with the hepatitis C virus (HCV) commonly causes persistent disease, which may lead to cirrhosis and hepatocellular carcinoma. The pathogenesis of HCV infection is not well understood, It is most like ly that both viral and host factors contribute to HCV persistence, Thi s review focuses on the host's immune response to HCV in an attempt to present the current knowledge and concepts of the interactions betwee n the virus and tile host during HCV infection. Expansion of B lymphoc ytes and antibody production to virtually any HCV protein can be detec ted in most infected patients, However, observations in HCV-infected h umans as web as experimental infections in chimpanzees suggest that na tural HCV infection does not induce protective immunity and reinfectio n can readily be demonstrated after inoculation with homologous or ind ependent strains in HCV-seroconverted animals, Nevertheless, the immun e system may gain partial control over HCV even in patients with chron ic infection, as HCV infection in severely inununocompromised patients runs a particular cholestatic course which may rapidly lead to death from liver failure, Cytotoxic CD8+ T lymphocyte responses to HCV prote ins have been characterized in peripheral blood and liver tissue and w ere found to be remarkably polyclonal and multispecific. Epitopes were identified on all of the putative HCV proteins, although only few maj or histocompatibility complex molecules mere considered restriction el ements, Immunoregulation may be particularly important in HCV infectio n, The HCV core and NS4 proteins appear to be most immunogenic for per ipheral blood lymphocytes, and NS4 specific CD4+ lymphocytes are prefe rentially compartmentalized to the liver, However, there is an inverse relationship between CD4+ lymphocyte responses and antibody levels in infected patients, Furthermore, a strong cellular response to the HCV core protein apparently favors a benign course of infection, This unu sual T-B cell relationship may be the consequence of an altered cytoki ne release during HCV infection, Alternatively, this virus may have fo und devices that can disturb immunoregulation in infected patients, A better understanding of these immunological mechanisms induced by HCV infection should make it possible to develop more effective strategies for the prevention and treatment of this insidious disease. (C) Europ ean Association for the Study of the Liver.