Accumulation of multiple T-cell clonotypes in the liver of primary biliary cirrhosis

Abstract

The histological hallmark of primary biliary cirrhosis (PBC) is the destruction of the interlobular and septal bile ducts accompanied by a dense accumulation of lymphocytes; this constellation of features is termed chronic nonsuppurative destructive cholangitis. To analyze the T cells responsible for bile duct destruction, the T-cell receptor (TCR) Vβ repertoire was studied in liver biopsy specimens, and also in peripheral blood lymphocytes (PBL) obtained from seven patients with PBC in the early stage (Scheuer's stage I or II). The complementary DNA (cDNA) of each TCR Vβ1-20 chain was amplified by reverse-transcription polymerase chain reaction (RT-PCR), and the PCR products were examined by single-strand conformation polymorphism (SSCP) analysis. On the RT-PCR/SSCP analysis, a leukemic cell line, HPB-ALL, showed bands in TCR Vβ 5.2 and Vβ 6, indicating clonal expansion with distinct TCR. In the PBL from healthy subjects, the PCR products were amplified from many TCR Vβ and were shown as smears on SSCP, suggesting that PBL consist of diverse T-cell clones. In PBC, many TCR Vβ products were amplified by RT-PCR in both liver tissues and PBL, and no biased expression of a particular Vβ was observed. SSCP analysis revealed multiple bands in most Vβ chains, suggesting the presence of selected but multiple T-cell clones. Both the number and types of Vβ showing clonal expansion were heterogeneous in the PBC patients. A comparative RT-PCR SSCP analysis of each TCR Vβ between tissue lymphocytes and PBL revealed the presence of some identical T-cell clones 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.(Hepatology 1997 Jan;25(1):33-7)