Life, activation and death of intrahepatic lymphocytes in chronic hepatitis C

The healthy liver of adult humans has little or no lymphocyte component and the histological finding of intrahepatic lymphocytes (IHL) is evidence of liver pathology. In a liver injured by chronic hepatitis C, the most common chronic liver disease, most IHL are activated/pro-inflammatory cells, whic h are particularly enriched for effectors of innate immunity (natural kille r (NK), natural T, and other NK-like T cells). IHL do not undergo clonal ex pansion in the liver but migrate from extrahepatic sites to the chronically infected liver, where they display effector function and subsequently die, suggesting that maintenance of the IHL pool depends on continuous lymphocy te migration. The cytotoxic and inflammatory functions of these IHL have th ree potential outcomes: 1) they could be helpful in clearing the virus (a r are case in hepatitis C virus (HCV) infection); 2) they could be useless an d have no effect on the infection; or 3) they could be harmful, whereby ove raggressive lymphocyte responses destroy the liver in a continuous and unsu ccessful attempt to clear the virus. Unfortunately, we do not know as of ye t which of these possibilities is the case and, therefore, a more complete picture of the intrahepatic immune response will be relevant to the develop ment of new therapeutic strategies against HCV. Additionally and from a mor e general perspective, due to the availability of biopsied material and the high prevalence (similar to 3%) of HCV infection worldwide, studying the c hronically inflamed liver of hepatitis C patients is an ideal model to inve stigate the poorly understood processes of lymphocyte trafficking, activati on and death to non-lymphoid sites of chronic inflammation in man.