VARIABLE GENE USAGE OF T-CELL RECEPTOR GAMMA-CHAIN AND DELTA-CHAIN TRANSCRIPTS EXPRESSED IN SYNOVIA AND PERIPHERAL-BLOOD OF PATIENTS WITH RHEUMATOID-ARTHRITIS

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, gamma-delta-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 gamma-delta-T cell receptors (TcRs) expressed in synovia and peripheral blood of patients with RA by using the polymerase chain reaction (PCR) to amplify TcR gamma- and delta-chain transcripts. Most patients showed no restriction in V-gamma-gene usage since synovial mononuclear cells (SMC) expressed TcR gamma-chain transcripts which used the same set of V-gamma-genes as peripheral blood mononuclear cells (PBMC). In contrast, the majority of patients expressed a restricted SMC V-delta-chain repertoire biased towards V-delta-1, but V-delta-2 mRNA transcripts were also detected, albeit at low levels in some patients. The TcR delta-chain repertoires of PBMC from healthy control subjects were also characterized. There was variation in the TcR delta-chain repertoires of PBMC from patients when compared with controls, particularly with respect to expression of V-delta-4. V-delta-4 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 gamma-delta-T cells in the rheumatoid synovium are reactive to Mycobacterium tuberculosis and that response to M. tuberculosis is restricted to V-gamma-9/V-delta-2-bearing T cells, if a superantigen is involved in the pathogenesis of RA.