Analysis of T cell receptor V alpha and V beta gene usage in synovia of patients with rheumatoid arthritis.

T cells are thought to play a fundamental role in the pathogenesis of rheumatoid arthritis (RA). Activated T cells expressing alpha/beta 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 alpha and/or V beta gene usage of the expressed alpha/beta Tcr repertoire is a feature of synovial T cells in patients with RA, the polymerase chain reaction (PCR) was used to amplify Tcr-alpha and Tcr-beta 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 alpha gene families was found. Similarly, most of the 18 Tcr V beta gene families could be detected in RA synovia although there were quantitative differences in Tcr V beta 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 alpha/beta 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.