T Cell Repertoire in Systemic Sclerosis

Abstract

An increase of certain T cell subsets in systemic sclerosis patients, particularly of V81⁺ γδ T cells in the blood and lungs and CD8⁺ αβ T cells in the lungs, has been shown. The diversity of T cell antigen receptor (TCR) Vδ1, Vα, and Vβ 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 Vα and Vβ 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 Vδ1 transcripts and in different Vα and Vβ gene families. Limited Vδ1-Cδ junctional region lengths were observed in the patients compared to controls. This was confirmed by sequence analysis of Vδ1-Cδ 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 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.

Key Words:

• systemic sclerosis
• T cell subsets
• bronchoalveolar lavage
• T cell receptor
• diversity
• polymerase chain reaction