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Association of clonally expanded T cells with the syndrome of primary biliary cirrhosis and limited scleroderma

Clinical features of the CREST (calcinosis cutis, Raynaud's syndrome, esophageal dysmotility, sclerodactyly, and telangiectasias) syndrome are sometimes exhibited in patients with primary biliary cirrhosis (PBC), but the postulated autoimmune mechanisms behind these conditions are poorly understood. Clonally expanded T cells may play an important role in disease pathogenesis. In this study, overrepresentation of one T‐cell receptor beta chain variable region, TCRBV3, was documented in patients with PBC and/or CREST. Overrepresentation of the TCRBV3 gene mRNA was demonstrated by semiquantitative reverse‐transcriptase polymerase chain reaction (RT‐PCR). T cells expressing TCRBV3 were analyzed by flow cytometry, were primarily CD8+, and contained activated cells as assessed by expression of CD69. Clonally expanded T cells within this population were documented by both complementarity determining region 3 (CDR3) length polymorphism analysis and sequencing of T‐cell receptor CDR3 cDNA. TCRBV3+ clonal expansions were stable when followed for up to 5 years. The results of this study demonstrate that the T‐cell repertoire of patients with PBC and CREST is characterized by expanded clonal populations of CD8+ TCRBV3+ T cells. These clonal expansions provide evidence that stimulation of clonal populations of CD8+ T cells is associated with the clinical syndrome of PBC with CREST.