The Repertoire of T-Cell Receptors in Systemic Sclerosis

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Abstract
Certain T cell subsets are increased in systemic sclerosis patients, particularly Vδ1+ γδ T cells in the blood and lungs and CD8+ αβ T cells in the lungs. The repertoires of T cell antigen receptor (TCR) Vδl, Vα, and Vβ gene families were examined by two methods of analysis. First, the relative abundance of Vα and Vβ gene transcripts was determined in the blood and bronchoalveolar fluid of the patients. Second, the diversity of the junctional regions in TCR Vδl transcripts and in different Vα and Vβ gene families was analyzed. Limited Vδ-Cδ junctional region lengths were observed in the patients compared with controls. This was confirmed by sequence analysis of Vδ1-Cδ junctional regions after subcloning amplified products in a bacterial vector. Evidence for selection of the Vδl+ T cells in the tissues of patients came from the findings that the same Vδ1-Cδ 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 Vα and Vβ gene families, particularly within bronchoalveolar CD8+ T cell subset. These data suggest that the oligoclonal expansion of the corresponding αβ and γδ T cells is antigen-driven and may be important in the pathogenesis of systemic sclerosis.

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