ANALYSIS OF PERIPHERAL-BLOOD MONONUCLEAR CELL STIMULATED WITH PYRUVATE-DEHYDROGENASE COMPLEX, T-CELL RECEPTORS FROM PATIENTS WITH PRIMARY BILIARY-CIRRHOSIS

Progressive destruction of the intrahepatic bile ducts in patients wit h primary biliary cirrhosis (PBC) is thought to be mediated by cytotox ic T cells which recognize certain epitopes, such as the pyruvate dehy drogenase complex (PDC). To clarify the T-cell repertoire in PBC, we a nalyzed T-cell receptor (TCR) V beta-chain messages expressed in perip heral blood mononuclear cells (PBMCs) stimulated with PDC and in liver biopsy specimens. PBMCs from 12 PBC patients and 6 healthy controls w ere examined. The TCR V beta repertoires of unstimulated PBMCs and PBM Cs stimulated with PDC purified from bovine heart were analyzed, using the reverse transcriptase-polymerase chain reaction (RT-PCR) and sing le-strand conformation polymorphism (SSCP). Liver biopsy specimens fro m 5PBC patients were also analyzed. In the PBC patients, several diffe rent T-cell clones, some of which showed the same mobility, were evide nt in both the PDC-stimulated and unstimulated PBMCs, as demonstrated by SSCP analysis. In addition, TCR clonality of infiltrating lymphocyt es in the liver was also observed in PBC patients, showing common clon al T-cell accumulation with that seen in PBMCs stimulated with PDC. Th ese data indicate that common clonal T-cell accumulation specific for PDC may be present in both peripheral PBMCs and the liver of patients with PBC.