Clonal heterogeneity of synovial fluid T lymphocytes from patients with rheumatoid arthritis (original) (raw)

A Minority of Patients with Rheumatoid Arthritis Show a Dominant Rearrangement of T-Cell Receptor beta Chain Genes in Synovial Lymphocytes

Scandinavian Journal of Immunology, 1987

with Rheumatoid Arthrilis Show a Dominanl Rearrangement of T-Cel I Receplor/y Chain Genes in Synovial Lymphocytes. SCCUKL J. Immunol. 25,624-6.15. \^iil The clonality of T lymphocytes isolated from the synovial fluid and peripheral hlood nl palicnts with rheumatoid arthritis was invcsii^atcd hy rcMriction cn/.yme fragmcnl mappinj; ol the rearrangemenis ol' the/:f chain gone ol' Ihc r-ccll antigen reeeptor. Three patients showed a dominant rearrangement amonust their synovial fluid "I cells which «as not seen in their peripheral hlood T-ccll population, sugjiesiing the prfscncc ol a predominaiini; I-cell clone. However, most of ilie paiicnis examined (S out tif 11) denion>trated polycional 1-ecM populations in hoth their synovial lluid and peripheral hlood. Of four synovial Huid l-cell lines investit;iiled. one showed evidence of a domiiiimt T-ccil clone.

Lack of T cell oligoclonality in enzyme-digested synovial tissue and in synovial fluid in most patients with rheumatoid arthritis

Clinical & Experimental Immunology, 2008

The dominant presence of specific T-ectl populations in the rheumatoid joint as detected by Southern blot analysis ofT cell receptor (TCR) gene rearrangements would indicate local antigen recognition and T cell proliferation. We therefore studied TCR /{chain gene rearrangements using a C/*2 probe in paired samples ofT cell populations from synovial tissue and peripheral blood (/j = 6) as well as synovial fluid («=16) and peripheral blood («=18) of patients with rheumatoid arthritis (RA). Peripheral blood mononuclear cells from healthy donors {ri-7) served as a control. T cells were studied directly after isolation or after non-specific expansion with OKT3 monoclonal antibody (MoAb) and T cell growth factor (TCGF). DNA samples were digested with EcoR\ and IlindUl to detect rearrangements to C/il andC/i2, respectively. Extra bands were detected in all /ftvjRI-digested DNA samples prepared fVom both freshly isolated and non-specifically expanded T cell populations of patients and healthy donors, possibly representing "common" (V-) D-J rearrangements. Dominant rearrangements were found in only two out of 16 synovial fluid T cell populations (one freshly isolated and one expanded) and not in peripheral blood or synovial tissue derived T cell populations, No extra bands were detected in ///rtdlll-digcsted DNA samples. To investigate the effect of in vitro culture techniques on rearrangement patterns we studied DNA samples prepared from synovial tissue T cells obtained both by outgrowth from tissue with TCGF or by enzyme digestion and subsequent expansion either with TCGF or with OKT3 MoAb and TCGF. Whereas the latter Tcell population yielded "common" rearrangements, the former T cell populations yielded different dominant rearrangements. These data indicate that oligoclonality of the T cell populations in synovial tissue and synovial fluid of patients with RA is a rare event. The data also show the influence of m vitro culture techniques on the result of TCR gene rearrangement analysis.

Skewed T-cell receptor variable gene usage in the synovium of early and chronic rheumatoid arthritis patients and persistence of clonally expanded T cells in a chronic patient

Rheumatology (Oxford, England), 2000

Autoreactive T cells may contribute to the pathogenesis of rheumatoid arthritis (RA). We studied the T-cell receptor (TCR) V-gene repertoire in the blood and synovium of early and chronic RA patients using polymerase chain reaction-enzyme-linked immunosorbent assay to evaluate possible differences between these patient groups. Over-represented TCR V genes were observed in the synovium, but not in the blood of all RA patients (n = 38). The number of over-represented V genes was higher in the synovium of chronic RA patients (n = 31) than in that of early RA patients (n = 7). The V-gene profile was different among patients, and similar in the two knees for patients with bilateral synovitis (n = 5). The clonal composition of over-represented TCR BV genes in a patient with early RA and a patient with chronic RA was further studied by CDR3 region sequence analysis. A high level of clonal diversity was found in the joints and the blood of the early RA patient, suggesting a polyclonal T-cel...

Dominant and Shared T Cell Receptor β Chain Variable Regions of T Cells Inducing Synovial Hyperplasia in Rheumatoid Arthritis

Biochemical and Biophysical Research Communications, 1999

Previously, we demonstrated the presence of at least two distinct subpopulations of patients with rheumatoid arthritis (RA) employing a cell-transfer experiment using severe combined immunodeficient (SCID) mice. One group of patients, whose T cells derived from the rheumatoid joints, induced synovial hyperplasia (SH) in the SCID mice (the positive group). The other group did not display the induction of SH (the negative group). TCR/V␤ gene usage analysis indicated that some dominant T cell subpopulations were oligoclonally expanding only in the rheumatoid joints, and not in the periphery of the patients of the positive group. Moreover, these T cell subpopulations were not seen in the joints of patients in the negative group or in non-RA patients. In addition, the preferential uses of certain TCR/V␤s (V␤8, V␤12, V␤13, and V␤14) genes were demonstrated in these T cells. In this study, to investigate whether these T cells are driven by a certain antigen(s), the third complementarity determining regions (CDR3s) of TCR/V␤, especially V␤8 and V␤14 PCR products, were cloned and sequenced. As a result, a dominant CDR3 sequence, CASS-PRERAT-YEQ, was found in V␤14؉ T cells from the rheumatoid joint of a patient (Patient 1) of the positive group with a V␤14 skew. The identical CDR3 sequence also predominated in V␤14؉ T cells from the rheumatoid joint of another patient (Patient 7) of the positive group with a V␤14 skew. In addition, in the patients (Patients 4, 7, 8) of the positive group with a V␤8 skew, other dominant CDR3 sequences, CASS-ENS-YEQ and CASS-LTEP-DTQ, were found as in the case of V␤14. However, no identical CDR3 sequences were detected dominantly in the joints of the patients in the negative group or in non-RA patients. A V␤14؉ T cell clone (TCL), named G3, with the identical CDR3 sequence, CASS-PRERAT-YEQ, was isolated successfully from Patient 1, and cell transfer of G3 with autologous irradiated peripheral mononuclear cells induced SH in the SCID mice. Taken together, these results suggest that T cells inducing SH, thought to be pathogenic for RA, might be driven by a certain shared antigen(s).

Clonal dominance among synovial tissue-infiltrating lymphocytes in arthritis

Human Immunology, 1990

T-cell receptor gene rearrangement using a C beta probe was evaluated in 12 patients with rheumatoid arthritis, 2 with juvenile rheumatoid arthritis, and 1 with systemic lupus erythematosus, and in all the samples a dominant T-cell receptor gene rearrangement was noted. In rheumatoid arthritis identical T-cell receptor gene rearrangement was noted in freshly isolated synovial tissue-infiltrating lymphocytes (TIL) and the corresponding interleukin 2-propagated culture. TIL from five different joints obtained from one rheumatoid arthritis patient shared one dominant band, and TIL from three joints had an identical rearrangement. Limiting dilution experiments showed that 10% of T-cell clones had rearrangements matching the corresponding bulk in one rheumatoid arthritis patient. These findings lend further support to the suggestion that the clonal dominance noted among synovial tumor-infiltrating lymphocytes is the result of an in vivo process reflecting a selective T-cell receptor gene usage.

T cell receptor diversity and activation markers in the Vδ1 subset of rheumatoid synovial fluid and peripheral blood T lymphocytes

European Journal of Immunology, 1992

In the present study we have characterized the $6 T cell receptor (TcR) population in synovial fluid (SF) and peripheral blood (PB) of patients with chronic inflammatory arthritis. By double staining we have shown that (a) synovial Vsl+ cells have a high expression of activation markers CD45RO ("memory cells") and HLA-DR as compared to PB, indicating a preactivated population of VJ-carrying T cells in vivo and (b) interleukin 2-induced expansion of synovial cells yields a high proportion of y/6 in most samples expressing predominantly theVbl TcR. Junctional sequence analysis of theTcR 6 chain from interleukin 2-expanded PB cell lines demonstrated a polyclonal Vbl population in three out of three samples. In SF cell lines three out of four samples were polyclonally expanded. In SF from one patient, however, a limited repertoire of expressed V61 genes was found. Altogether, our data demonstrate the presence of preactivated VJ-expressing cells in the synovial compartment. This V61 population is predominantly polyclonal, except in one patient where oligoclonally expanded Val cells were detected.