T Cell Repertoire in Systemic Sclerosis

Abstract

An increase of certain T cell subsets in systemic sclerosis patients, particularly of V delta 1+ gamma delta T cells in the blood and lungs and CD8+ alpha beta T cells in the lungs, has been shown. The diversity of T cell antigen receptor (TCR) V delta 1, V alpha, and V beta gene repertoires was examined using reverse transcriptase-polymerase chain reaction to amplify rearranged TCR transcripts across the junctional region. This was followed by two methods of analysis. First, the relative expression of V alpha and V beta genes was determined in the blood and bronchoalveolar lavage fluid of the patients. Second, we looked for evidence of restricted diversity of the junctional regions in TCR V delta 1 transcripts and in different V alpha and V beta gene families. Limited V delta 1-C delta junctional region lengths were observed in the patients compared to controls. This was confirmed by sequence analysis of V delta 1-C delta junctional regions after subcloning amplified products in a bacterial vector. 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.