Analysis of T cell receptor Vα and Vβ gene usage in synovia of patients with rheumatoid arthritis

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Abstract
T cells are thought to play a fundamental role in the pathogenesis of rheumatoid arthritis (RA), Activated T cells expressing / T cell receptor (Tcr) infiltrate the rheumatoid synovium and could potentially initiate a local inflammatory response directed against joint constituents. A Tcr repertoire with restricted heterogeneity may reflect a selective expansion of T cells reactive to a few antigenic determinants within the synovium. To determine whether predominant V and/or V gene usage of the expressed / Tcr repertoire is a feature of synovial T cells in patients with RA, the polymerase chain reaction (PCR) was used to amplify Tcr- and Tcr- chain transcripts. The peripheral blood and synovia of five patients with adult RA were examined and no evidence of preferential use of 19 Tcr V gene families was found. Similarly, most of the 18 Tcr V gene families could be detected in RA synovia although there were quantitative differences in Tcr V gene expression when compared to peripheral blood. This report shows that when the extremely sensitive assay of oligonucleotide hybridization of PCR amplified Tcr transcripts is used, permitting identification of specific V gene families, the / Tcr repertoire in the rheumatoid synovium is more diverse than was previously thought. Therefore, in patients with RA of long duration, the synovial T cell response is most likely to be polyclonal.