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Most liver diseases are caused by host immune responses, and there have been many studies on the analysis of circulating lymphocyte subsets and their production of cytokines in patients with liver diseases. Although circulating lymphocytes are relatively easy to obtain and analyze, analysis of intrahepatic lymphocytes would be more important for understanding the immunopathogenesis of liver diseases, especially, viral hepatitis and autoimmune liver diseases. Two approaches are currently available to analyze intrahepatic lymphocytes in liver biopsy specimens, an immunohistochemical approach and a flow cytomeric analysis of isolated lymphocytes from liver tissues. Although use of an immunohistochemical approach would allow the distribution of particular lymphocyte subsets to be determined, quantitative estimation of infiltrating lymphocyte populations may be incorrect. In contrast, flow cytometry can determine the precise percentages of each lymphocyte population, but it does not provide any information on their intrahepatic distribution. The use of multiple antibodies to identify lymphocyte subsets can enable multi-color flow cytometric analysis, revealing the precise percentages of each subset, even those constituting an extremely minor subset of lymphocytes. Moreover, molecular biological approaches have been used to analyze the immunopathogenesis of liver diseases. This chapter summarizes findings obtained from the immunological analyses of biopsied liver tissues and how immunological analyses of liver biopsy specimens have contributed to the understanding of the immunopathogenesis of liver diseases. We also describe recent technical advances in the immunological analyses of liver biopsy specimens that can further enhance our understanding of the pathogenesis of liver diseases.

Immunological Analysis of Liver Diseases with Liver Biopsy Specimens