Analysis of T cell receptor repertoire in primary biliary cirrhosis

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T cells play an important role in the destruction of bile duct in primary biliary cirrhosis (PBC). To analyze the T cells responsible for this bile ductt destruction, the T cell receptor (TCR) V beta repertoire was studied in liver biopsy specimens, and also in peripheral blood lymphocytes (PBL) obtained from 9 patients with PBC in the early stage (Scheuer's Stage I or II). The cDNA of each TCR V beta _<1-20> chain was prepared and 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 V beta 5.2 and V beta 6, indicating clonal expansion with distinct TCR.In PBL from healthy subjects, PCR products were amplified in most TCRV beta and were demonstrated as smears on SSCP,suggesting that PBL consists of diverse T cell clones. In PBC,most TCR V beta products were also amplified by RT-PCR in both liver tissues and PBL,and no biased expression of a particular V beta was observed. SSCP analysis revealed multiple bands in most V beta chains, suggesting the presence of selected but multiple T cell clones. Both the number and types of V beta showing clonal expansion were heterogeneous in PBC patients, although an increased number of clones was identified in V beta 6. These results suggest that T cells infiltrating the liver in PBC consist of multiple clonotypes and that T cells with TCR V beta 6 may play some role in the pathogenesis of PBC.