Clonal analysis of liver-derived T cells of patients with primary biliary cirrhosis.
Lymphocyte infiltration in liver tissue is one important histological finding in primary biliary cirrhosis (PBC). So far, functional analyses of lymphocytes in PBC have focused on circulating lymphocytes, whereas lymphocytes at the involved site, the liver, have not been examined functionally. We have established interleukin 2 (IL-2)-dependent T lymphocyte lines (TLL) and clones (TLC) from liver biopsies of 14 patients with PBC. Phenotypic analysis using the monoclonal antibodies MT910 (CD2), MT811 (CD8), and MT151 (CD4) revealed that in nine of 14 TLL cytotoxic-suppressor T cells predominated (CD8+:52-84%; CD4+:14-48%), whereas in five of 14 TLL a preponderance of the CD4+ subpopulation was found (CD4+:56-73%; CD8+:28-45%). From 10 patients 137 TLC were generated which phenotypically correlated to the TLLs. We have tested the cytotoxic potential of seven TLL and 43 TLC in LDCC (lectin-dependent cell-mediated cytotoxicity), NK (natural killing) and ADCC (antibody-dependent cell-mediated cytotoxicity) assays. All TLL and all but one CD8+ TLC tested showed high activity in the LDCC assay, reflecting the cytolytic activity of cytotoxic T cells (CTL). CD4+ clones with LDCC activity were rarely found. NK activity and K cell activity could only be found in two clones. For the first time TLC and TLL from liver tissue of PBC patients could be generated. The high cytotoxic activity displayed by T cells derived from the liver indicates an important role for this immunological mechanism in the tissue damaging process.