Limited heterogeneity of rearranged T cell receptor Vα and Vβ transcripts in synovial fluid T cells in early stages of rheumatoid arthritis

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Abstract
Objective. The identification of activated T cells in synovial fluid and synovium, and the association of rheumatoid arthritis (RA) with specific HLA–DR restriction elements, strongly suggest that these T cells play a critical role in the etiology and pathogenesis of RA. Analysis of the T cell receptor (TCR) repertoire in the early stages of RA might be an approach to identify those T cells involved in the initiation and/or perpetuation of the disease. Methods. TCR Vα and Vβ transcripts of synovial T cells, sampled at the early stages of RA, were amplified by reverse transcriptase–polymerase chain reaction. HLA–DR subtyping was determined by serologic analysis and dot‐blot hybridization of polymerase chain reaction amplification products using digoxigenin‐labeled, sequence‐specific oligonucleotide probes. Results. Our findings showed a limited heterogeneity of Vα and Vβ TCRs in synovial fluid T cells, and a preferential usage of TCR Vα17 in early RA. In contrast, in the later stages of RA, a more polyclonal TCR V α and V β gene usage was observed. Conclusion. Our results support the view that induction of RA is driven by an oligoclonal immune response to an unknown antigen. These findings also suggest a pathogenetic role for Vα17 T cells in the early stages of RA.