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

Abstract

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 Vγ gene usage since synovial mononuclear cells (SMC) expressed TcR γ‐chain transcripts which used the same set of Vγ genes as peripheral blood mononuclear cells (PBMC). In contrast, the majority of patients expressed a restricted SMC Vδ‐chain repertoire biased towards Vδ1, but Vδ2 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.

A high proportion of the Vδ1+ synovial fluid γδ T cells in juvenile rheumatoid arthritis patients express the very early activation marker CD69, but carry the high molecular weight isoform of the leucocyte common antigen (CD45RA)

“…We have previously shown that the majority of synovial yd T cells in JRA patients express the Vi51J51/2 gene products, whereas only a minor proportion uses the Vdl gene segment [2]. Similar results have also been reported in RA [3][4][5][6][7]. In JRA patients we also detected H LA-DR and the very early activation antigen CD69 [23] on synovial yd T cells.…”

“…Most of these eells express the a/i T cell receptor whereas a small proportion (5-15%) express the yd T cell receptor. It is established that the afi T cells recognize antigen in context with MHC class I or class II molecules, but for the yd T cells little is known eoneerning expression of activation markers, activation requirements, antigenic repertoire and restriction elements used, yd T cells have been studied in a number of pathological conditions such as RA and JRA [2][3][4][5][6][7], leprosy [8], polymyositis [9], eoeliac disease [10][11], eancer [12][13][14], primary immunodeficiency syndrome [15,16], Behijet's disease [17], and infections with Epstein-Barr virus [18] and HIV-1 [19]. Promiscuous cytotoxicity exerted by yd T cells has been documented in vitro [20,21] Correspondence: Dr Jens Kjeldsen-Kragh, Red Cross and National Hospital Blood Centre, PO Box 6739, St Olavs Plass, N-0130 Oslo, Norway.…”

The γδ T cell repertoire in Graves' disease and multinodular goitre

“…MA). Membranes were hybridized as described previously [26] with an internal Cii oligonucleotide (C<S3 of [10]), Densitoinetry of hybridized bands was carried out using the Bio-Proltle Image Analysis System (Version 4,01. Vilbcr-Lourmat, France).…”

Predominance of T cell receptor Vδ3 in small bowel biopsies from celiac disease patients

“…Streptococcus pyogenes and Listeria monocytogenes [24]. Hsp65-responsive 7^ T cells cross-reactive with a synovial antigen can be cloned from joint aspirates of patients with rheumatoid arthritis [25,26], and the 7(5 T cells which are found in rheumatic joints have been shown to be oligoclonal [12]. Antibodies against various hsp have been reported in autoimmune diseases, including type I diabetes [27], autoimmune thyroid disease [28] and systemic lupus erythematosus [29].…”

“…Primers used for TCR V7 and TCR V(5 subfamilies were those described by Olive et al [12], consisting of four 7 and six S variable region oligonucleotides and one each of 5 and 7 constant region primers (Table 1). PCR conditions for biopsy tissue and PBMC were identical.…”