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

Savill, Corinne M.; Delves, Peter J.; Kioussis, Dimitris; Walker, P.R.; Lydyard, Peter M.; Colaco, B.; Shipley, Michael; Im, Roitt

doi:10.1111/j.1365-3083.1987.tb01089.x

Cited by 75 publications

(29 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results are compatible with previous reports of clonal heterogeneity of Tcr-P chain gene rearrangements in synovial fluid (14)(15)(16), membrane (16) and a polycional T cell infiltrate. In the earlier studies based on detection of Tcr-p chain gene rearrangements by Southern blotting, specific V genes could not be identified.…”

Section: Discussionsupporting

confidence: 93%

Analysis of T cell receptor V_α and V_β gene usage in synovia of patients with rheumatoid arthritis

Olive

1991

Immunology & Cell Biology

View full text Add to dashboard Cite

Summary T cells are thought to play a fundamental role in the pathogenesis of rheumatoid arthritis (RA), Activated T cells expressing α/β T cell receptor (Tcr) infiltrate the rheumatoid synovium and could potentially initiate a local inflammatory response directed against joint constituents, A Tcr repertoire with restricted heterogeneity may reflect a selective expansion of T cells reactive to a few antigenic determinants within the synovium. To determine whether predominant Vα and/or Vβ gene usage of the expressed α/β Tcr repertoire is a feature of synovial T cells in patients with RA, the polymerase chain reaction (PCR) was used to amplify Tcr‐α and Tcr‐β chain transcripts. The peripheral blood and synovia of five patients with adult RA were examined and no evidence of preferential use of 19 Tcr Vα gene families was found. Similarly, most of the 18 Tcr Vβ gene families could be detected in RA synovia although there were quantitative differences in Tcr Vβ gene expression when compared to peripheral blood. This report shows that when the extremely sensitive assay of oligonucleotide hybridization of PCR amplified Tcr transcripts is used, permitting identification of specific V gene families, the α/β Tcr repertoire in the rheumatoid synovium is more diverse than was previously thought. Therefore, in patients with RA of long duration, the synovial T cell response is most likely to be polyclonal.

show abstract

Section: Discussionsupporting

confidence: 93%

Analysis of T cell receptor V_α and V_β gene usage in synovia of patients with rheumatoid arthritis

Olive

1991

Immunology & Cell Biology

View full text Add to dashboard Cite

show abstract

“…It has been proposed that mycobacterial antigens are important in RA since mycobacterial reactive clones have been isolated from synovia (31). However, synovial T cells do not always appear to be clonally restricted in their T-cell receptor usage and this argues against a single local antigen response (32)(33)(34)(35)(36)(37). Lymphocytes can also reach inflammatory sites in other ways: by recognition of inflammatory endothelium (26) or by chemotaxis toward factors released by activated cells.…”

Section: Discussionmentioning

confidence: 99%

Perforin and granzyme A expression identifying cytolytic lymphocytes in rheumatoid arthritis.

Griffiths

Alpert

Lambert

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Lymphocytes from the synovial fluid of patients with rheumatoid arthritis were examined for the expression of granzyme A and perforin. Previous studies have demonstrated that the expression of these proteins, which are implicated as mediators of cytotoxicity, can be used to identify putative cytolytic lymphocytes in vivo. Twenty-two synovial fluid samples were analyzed by in situ hybridization and immunohistochemistry. In six patients receiving low doses of immunosuppressant, a population of granzyme A-and perforin-expressing lymphocytes could be identified. In contrast, lymphocytes from patients who were receiving high doses of immunosuppressant did not contain any granzyme A-or perforin-expressing lymphocytes. Synovial fluid lymphocytes from patients with osteoarthritis did not express either marker.

show abstract

“…The inverse PCR, therefore, is a more potent tool for the study of TCR repertoires in human diseases such as multiple sclerosis (24,25), Graves disease (46,47), primary biliary cirrhosis (48), allograft rejection (23,49), sarcoidosis (50), malignant disease (26), Crohn disease (51), and RA (5)(6)(7)(8)(9)(10)(11) To analyze whether the most abundant Va and V(3 gene segments identified in the productively rearranged genes were enriched in the synovial fluid as compared to the peripheral blood repertoire, we hybridized cDNA libraries generated by the inverse PCR with specific oligonucleotides.…”

Section: Discussionmentioning

confidence: 99%

The T-cell-receptor repertoire in the synovial fluid of a patient with rheumatoid arthritis is polyclonal.

Uematsu

Wege

Straus

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

148

View full text Add to dashboard Cite

We have analyzed the T-cell-receptor repertoire expressed in the synovial fluid of a patient with rheumatoid arthritis by using an inverse polymerase chain reaction. Total RNA was isolated from Ficoll-purifled mononuclear cells and converted into circularized double-stranded cDNA. Specific amplification of a-and E-chain variable regions (Va and VP) was achieved with inverted a-and 3-chain constant region (Ca and C13) primer pairs, and the amplification products were cloned into phage vectors. A total of 78 a and 7618 clones were sequenced, and 67 and 72 productively rearranged a and 13 genes were identified, respectively. Thirty-one Va, 33 a-chain joining region (Ja), 29 VP3, and 12 13-chain joining region (J13) gene segments were found in the productively rearranged clones, indicating that the T-cell repertoire expressed in the synovial fluid of this RA patient is highly heterogenous and polyclonal. Comparison of peripheral blood and synovial fluid repertoires showed that the most abundant V13 sequences, V132.1 and V133

show abstract

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

Cited by 75 publications

References 22 publications

Analysis of T cell receptor V_α and V_β gene usage in synovia of patients with rheumatoid arthritis

Analysis of T cell receptor V_α and V_β gene usage in synovia of patients with rheumatoid arthritis

Perforin and granzyme A expression identifying cytolytic lymphocytes in rheumatoid arthritis.

The T-cell-receptor repertoire in the synovial fluid of a patient with rheumatoid arthritis is polyclonal.

Contact Info

Product

Resources

About

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

Cited by 75 publications

References 22 publications

Analysis of T cell receptor Vα and Vβ gene usage in synovia of patients with rheumatoid arthritis

Analysis of T cell receptor Vα and Vβ gene usage in synovia of patients with rheumatoid arthritis

Perforin and granzyme A expression identifying cytolytic lymphocytes in rheumatoid arthritis.

The T-cell-receptor repertoire in the synovial fluid of a patient with rheumatoid arthritis is polyclonal.

Contact Info

Product

Resources

About

Analysis of T cell receptor V_α and V_β gene usage in synovia of patients with rheumatoid arthritis

Analysis of T cell receptor V_α and V_β gene usage in synovia of patients with rheumatoid arthritis