Perforin and granzyme B lytic protein expression during chronic viral and autoimmune hepatitis

Background. Cytotoxic T lymphocytes and Kupffer cells are essential compone nts of the immune response during liver diseases. Recent studies have highl ighted the role of cytotoxic T lymphocytes using Fas and its ligand in indu ced hepatocyte death during acute and chronic hepatitis. Methods. In the pr esent work, the main purpose was to investigate perforin and granzyme B exp ression in liver biopsies of patients with chronic hepatitis (10 HBV, 14 HC V and 10 autoimmune hepatitis) using immunohistochemistry. The liver biopsi es of two normal individuals were also studied in the same conditions. Resu lts. Few intrahepatic T lymphocytes expressed perforin and granzyme B, whil e a large number of Kupffer cells were positive for both proteins in all th e patients tested. The co-localization of perforin and granzyme B, and CD3 or CD68 antigens was visualized, respectively, in T cells and Kupffer cells , using confocal microscopy. In situ hybridization assays confirmed that pe rforin and granzyme B mRNAs were present in the liver during chronic hepati tis. The results were similar among the three groups of patients and whatev er the activity of the disease. Perforin and granzyme B expression was lack ing in liver samples from normal individuals. Conclusions. These data sugge st a minor role for the T cell-mediated perforin/granzyme B death pathway, and a putative role for Kuppfer cells via lytic protein release, during chr onic hepatitis.