LYMPHOCYTE-T FROM PATIENTS WITH PRIMARY BILIARY-CIRRHOSIS PRODUCE REDUCED AMOUNTS OF LYMPHOTOXIN, TUMOR-NECROSIS-FACTOR AND INTERFERON-GAMMA UPON MITOGEN STIMULATION

Primary biliary cirrhosis (PBC) is considered an autoimmune disease characterized by destruction of small intrahepatic bile ducts by lymphocytes. Altered functions of these lymphocytes might reflect an abnormal immune response leading to tissue damage. We investigated lymphokine secretion by mitogen-stimulated T lymphocytes from the liver biopsies of patients with PBC and for comparison also peripheral blood. In PBC, diminished synthesis of lymphotoxin (TNF-beta), tumor necrosis factor (TNF-alpha) and interferon-gamma (IFN-gamma) was found both in T-cell lines from liver tissue and in peripheral blood. The reduction was most prominent for TNF-beta in early histological stages of PBC, and appeared to be a stable phenomenon when T cells were tested after long-term tissue culture. Analysis of mRNA levels indicates a possible link between reduced TNF-beta production and a defect in interleukin-2 transcription. The data suggest that diminished lymphokine production in patients with PBC may play an important role in the immunopathogenesis of this disease.