Variable gene usage of T cell receptor gamma- 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.
Olive
C
C
Division of Clinical Sciences, John Curtin School of Medical Research, Australian National University, Canberra, Australia.
Gatenby
P A
PA
Serjeantson
S W
SW
D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001483:Base Sequence; D003208:Concanavalin A / Q000494:pharmacology; D015870:Gene Expression; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor / Q000235:genetics; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D006801:Humans; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics*; D013582:Synovial Fluid / Q000166:cytology; D013601:T-Lymphocytes / Q000502:physiology*
D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D016692:Receptors, Antigen, T-Cell, gamma-delta; D003208:Concanavalin A