THE REPERTOIRE OF T-CELL RECEPTORS IN SYSTEMIC-SCLEROSIS

Certain T cell subsets are increased in systemic sclerosis patients, particularly V delta 1(+) gamma delta T cells in the blood and lungs and CD8(+) alpha beta T cells in the lungs. The repertoires of T cell antigen receptor (TCR) V delta 1, V alpha, and V beta gene families were examined by two methods of analysis. First, the relative abundance of V alpha and V beta gene transcripts was determined in the blood and bronchoalveolar fluid of the patients. Second, the diversity of the junctional regions in TCR V delta 1 transcripts and in different V alpha and V beta gene families was analyzed. Limited V delta 1-C delta junctional region lengths were observed in the patients compared with controls. This was confirmed by sequence analysis of V delta 1-C delta junctional regions after subcloning amplified products in a bacterial vector. Evidence for selection of the V delta 1(+) T cells in the tissues of patients came from the findings that the same V delta 1-C delta junctional sequences persisted in an individual patient over time and that identical junctional sequences were isolated from multiple sites. A restricted diversity of the junctional region lengths was also detected in a number of V alpha and V beta gene families, particularly within bronchoalveolar CD8(+) T cell subset. These data suggest that the oligoclonal expansion of the corresponding alpha beta and gamma delta T cells is antigen-driven and may be important in the pathogenesis of systemic sclerosis.