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.
TCR V alpha and V beta 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.
Our findings showed a limited heterogeneity of V alpha and V beta TCRs in synovial fluid T cells, and a preferential usage of TCR V alpha 17 in early RA. In contrast, in the later stages of RA, a more polyclonal TCR V alpha and V beta gene usage was observed.
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 V alpha 17 T cells in the early stages of RA.