ACCUMULATION OF MULTIPLE T-CELL CLONOTYPES IN THE LIVER OF PRIMARY BILIARY-CIRRHOSIS

The histological hallmark of primary biliary cirrhosis (PBC) is the de struction of the interlobular and septal bile ducts accompanied by a d ense accumulation of lymphocytes; this constellation of features is te rmed chronic nonsuppurative destructive cholangitis, To analyze the T cells responsible for bile duct destruction, the T-cell receptor (TCR) V beta repertoire was studied in liver biopsy specimens, and also in peripheral blood lymphocytes (PBL) obtained from seven patients with P BC in the early stage (Scheuer's stage I or II), The complementary DNA (cDNA) of each TCR V beta(1-20) chain was amplified by reverse-transc ription polymerase chain reaction (RT-PCR), and the PCR products were examined by single-strand conformation polymorphism (SSCP) analysis, O n the RT-PCR/SSCP analysis, a leukemic cell line, HPB-ALL, showed band s in TCR V beta 5.2 and V beta 6, indicating clonal expansion with dis tinct TCR, Ln the PBL from healthy subjects, the PCR products were amp lified from many TCR V beta and were shown as smears on SSCP, suggesti ng that PBL consist of diverse T cell clones, In PBC, many TCR V beta products were amplified by RT-PCR in both liver tissues and PBL, and n o biased expression of a particular V beta was observed, SSCP analysis revealed multiple bands in most V beta chains, suggesting the presenc e of selected but multiple T-cell clones, Both the number and types of V beta showing clonal expansion were heterogeneous in the PBC patient s, A comparative RT-PCR SSCP analysis of each TCR V beta between tissu e lymphocytes and PBL revealed the presence of some identical T-cell c lones in both the PBC liver and the PBL, These results suggest that T cells infiltrating the liver in PBC consist of multiple clonotypes and that T-cell clones accumulated in the Liver are also present in PBL.