Tγδ Cells and their Subsets in Blood and Synovial Tissue from Rheumatoid Arthritis Patients

Abstract

We have examined the frequencies of T gamma delta cells in blood, synovial fluids, and synovial membranes of patients with rheumatoid arthritis (RA) and in blood from age-matched controls. Immunocytochemical and immunohistochemical techniques were used with monoclonal antibodies BB3 and A13 to define a major and minor blood subset of T gamma delta cells respectively. Together, these antibodies identify the majority (if not all) of the peripheral blood T gamma delta cells. Significantly lower levels of T gamma delta cells were found in the blood of RA patients compared with controls, whilst higher but not significant numbers were found in the synovial fluids of paired samples. Scattered T gamma delta cells were found only in some synovial membranes with a distribution similar to the T alpha beta cells. Analysis of the two different T gamma delta-cell subsets indicated a ratio of BB3 to A13 of about 5:1 in control and RA blood. However, this ratio was less than 1:1 in the RA synovial fluids and membranes. The migratory nature of the A13+ cells could account for their predominance in these sites. The possible pathological significance of these cells in the rheumatoid synovial fluid and synovial membranes is discussed.

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.…”

Distinct immunologic features of finnish Sjögren's syndrome patients with HLA alleles DRB1*0301, DQA1*0501, and DQB1*0201. Alterations in circulating T cell receptor γ/δ subsets

“…There is evidence that, in addition to the small bowel mucosa in patients with celiac disease, Val + T cells are enriched in the synovial membrane and synovial fluid in rheumatoid arthritis (36,37). According to a recent study, these cells could play a significant role in the destruction of joints in rheumatoid arthritis, since they may be directly cytotoxic to the cells that comprise the joint structure (38).…”

Elevation of activated γδ T cell receptor bearing T lymphocytes in patients with autoimmune chronic liver disease

“…Tbe elevation of A13+ y6J cells in patients witb AI-CAH or PSC suggests that Cy2/56\/'V6\ genes may bave undergone rearrangement. It has been described that this subtype of yS'*' T cells is over-represented in the peripheral blood, synovial membrane and synovial fluid of patients with rheumatoid arthritis [5,15], in the gastrointestinal tract of patients with coeliac disease [15][16][17] and also in the peripheral blood of patients with common variable immunodeficiency or patients infected witb HIV [18][19][20]. These findings may suggest that activation of tbis subset of y^+ T cells characteristically occurs in response to both endogenous stimuli, such as autoantigens, and exogenous, sucb as viruses or bacteria.…”