Variable gene usage of T cell receptor γ‐ and δ‐chain transcripts expressed in synovia and peripheral blood of patients with rheumatoid arthritis

SUMMARY The synovial tissue and fluid of patients with rheumatoid arthritis (RA) contain activated T cells that probably have a central role in the disease process which leads to joint destruction. A subset of T cells, γδ T cells detected at the site of inflammation, may be important in the pathogenesis of the disease. This study investigated variable (V) gene usage of γδ T cell receptors (TcRs) expressed in synovia and peripheral blood of patients with RA by using the polymerase chain reaction (PCR) to amplify TcR γ‐and γ‐chain transcripts. Most patients showed no restriction in V γ gene usage since synovial mononuclear cells (SMC) expressed TcR γ‐chain transcripts which used the same set of V γ genes as peripheral blood mononuclear cells (PBMC). In contrast, the majority of patients expressed a restricted SMC Vδ‐chain repertoire biased towards Vδ1, but Vδ 2 mRNA transcripts were also detected, albeit at low levels in some patients. The TcR δ‐chain repertoires of PBMC from healthy control subjects were also characterized. There was variation in the TcR δ‐chain repertoires of PBMC from patients when compared with controls, particularly with respect to expression of Vδ4. Vδ4 mRNA transcripts were expressed in PBMC of only two of seven RA patients in contrast with eight of the nine controls (P=0.03). These findings are compatible with reports that γδ T cells in the rheumatoid synovium are reactive to Mycobacterium tuberculosis and that response to M. tuberculosis is restricted to VγL9/Vδ2‐bearing T cells, if a superantigen is involved in the pathogenesis of RA.