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Skewed T-cell receptor BV14 and BV16 expression and shared CDR3 sequence and common sequence motifs in synovial T cells of rheumatoid arthritis

Genes & Immunity volume 6, pages 248–261 (2005)Cite this article

Abstract

T-lymphocytes play an important role in rheumatoid arthritis (RA). In this study, we evaluated the hypothesis that common T-cell receptor (TCR) structural features may exist among infiltrating T cells of different RA patients, if the TCR repertoire is shaped by interaction with common self or microbial antigens in the context of susceptible HLA genes in RA. Synovial lesion tissue (ST), synovial fluid (SF) and blood specimens from RA patients and controls were analyzed for TCR V gene repertoire by real-time PCR. There was highly skewed BV14 and BV16 usage in synovial T cells of RA as opposed to those of controls, which was accompanied with a trend for correlation between skewed BV16 and DRB1*0405. Immunoscope analysis of the V–D–J region of ST-derived T cells demonstrated oligoclonal and polyclonal expansion of BV14+ and BV16+ T cells. Detailed characterization using specific BV and BJ primers further revealed common clonotypes combining the same BV14/BV16, BJ and CDR3 length. DNA cloning and sequence analysis of the clonotypes confirmed identical CDR3 sequences and common CDR3 sequence motifs among different RA patients. The findings are important in the understanding of BV gene skewing and CDR3 structural characteristics among synovial infiltrating T cells of RA.

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References

  1. Lee DM, Weinblatt ME . Rheumatoid arthritis. Lancet 2001; 358: 903–911.

    Article  CAS  PubMed  Google Scholar 

  2. Lipsky PE, Davis LS . The central involvement of T cells in rheumatoid arthritis. Immunologist 1998; 6: 121–129.

    CAS  Google Scholar 

  3. Kerlan-Candon S, Combe B, Vincent R, Clot J, Pinet V, Eliaou JF . HLA-DRB1 gene transcripts in rheumatoid arthritis. Clin Exp Immunol 2001; 124: 142–149.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. MacGregor A, Ollier W, Thomson W, Jawaheer D, Silman A . HLA-DRB1*0401/0404 genotype and rheumatoid arthritis: increased association in men, young age at onset, and disease severity. J Rheumatol 1995; 22: 1032–1036.

    CAS  PubMed  Google Scholar 

  5. Fries JF, Wolfe F, Apple R et al. HLA-DRB1 genotype associations in 793 white patients from a rheumatoid arthritis inception cohort: frequency, severity, and treatment bias. Arthritis Rheum 2002; 46: 2320–2329.

    Article  CAS  PubMed  Google Scholar 

  6. Dolhain RJ, van der Heiden AN, ter Haar NT, Breedveld FC, Miltenburg AM . Shift towards T lymphocytes with a T helper 1 cytokine profile in the joints of patients with rheumatoid arthritis. Arthritis Rheum 1996; 12: 1961–1969.

    Article  Google Scholar 

  7. Berner B, Akca D, Jung T, Muller GA, Reuss-Borst MA . Analysis of Th1 and Th2 cytokines expressing CD4+ and CD8+ T cells in rheumatoid arthritis by flow cytometry. J Rheumatol 2000; 27: 1128–1135.

    CAS  PubMed  Google Scholar 

  8. Davis LS, Cush JJ, Schultz-Koops H, Lipsky PE . Rheumatoid synovial CD4+ T cells exhibit a reduced capacity to differentiate into IL-4 poducing T helper-2 effector cells. Arthritis Res 2001; 3: 54–64.

    Article  CAS  PubMed  Google Scholar 

  9. Goronzy JJ, Bartz-Bazzanella P, Hu W, Jendro MC, Walser-Kuntz DR, Weyand CM . Dominant clonotypes in the repertoire of peripheral CD4+ T cells in rheumatoid arthritis. J Clin Invest 1994; 94: 2068–2076.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Struyk L, Kurnick JT, Hawes GE et al. T-cell receptor V-gene usage in synovial fluid lymphocytes of patients with chronic arthritis. Hum Immunol 1993; 37: 237–251.

    Article  CAS  PubMed  Google Scholar 

  11. Gonzalez-Quintial R, Baccala R, Pope RM, Theofilopoulos AN . Identification of clonally expanded T cells in rheumatoid arthritis using a sequence enrichment nuclease assay. J Clin Invest 1996; 97: 1335–1343.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Alam A, Lambert N, Lule H et al. Persistence of dominant T cell clones in synovial tissues during rheumatoid arthritis. J Immunol 1996; 156: 3480–3485.

    CAS  PubMed  Google Scholar 

  13. Londei M, Savill CM, Verhoef A et al. Persistence of collagen type II-specific T-cell clones in the synovial membrane of a patient with rheumatoid arthritis. Proc Natl Acad Sci USA 1989; 86: 636–640.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Pope RM, Pahlavani MA, LaCour E, Sambol S, Desai BV . Antigen specificity of rheumatoid synovial fluid lymphocytes. Arthritis Rheum 1989; 32: 1371–1380.

    Article  CAS  PubMed  Google Scholar 

  15. Devereux D, O'Hehir RE, McGuire J, van Schooten WC, Lamb JR . HLA-DR4Dw4-restricted T cell recognition of self antigen(s) in the rheumatoid synovial compartment. Int Immunol 1991; 3: 635–640.

    Article  CAS  PubMed  Google Scholar 

  16. Res PC, Struijk L, Leow A, Daha MR, van den Elsen PC, Breedveld FC . Inflamed joints of patients with rheumatoid arthritis contain T cells that display in vitro proliferation to antigens present in autologous synovial fluid. Functional analysis on the basis of synovial-fluid-reactive T cell clones and lines. Hum Immunol 1994; 40: 291–298.

    Article  CAS  PubMed  Google Scholar 

  17. Paliard X, West SF, Lafferty JA et al. Evidence for the effects of a superantigen in rheumatoid arthritis. Science 1991; 253: 325–329.

    Article  CAS  PubMed  Google Scholar 

  18. Holoshitz J, Klajman A, Drucker I et al. T lymphocytes of rheumatoid arthritis patients show augmented reactivity to a fraction of mycobacteria cross-reactive with cartilage. Lancet 1986; 2: 305–309.

    Article  CAS  PubMed  Google Scholar 

  19. Zagon G, Tumang JR, Li Y, Friedman SM, Crow MK . Increased frequency of V beta 17-positive T cells in patients with rheumatoid arthritis. Arthritis Rheum 1994; 37: 1431–1440.

    Article  CAS  PubMed  Google Scholar 

  20. Alam A, Lule J, Coppin H et al. T-cell receptor variable region of the beta-chain gene use in peripheral blood and multiple synovial membranes during rheumatoid arthritis. Hum Immunol 1995; 42: 331–339.

    Article  CAS  PubMed  Google Scholar 

  21. VanderBorght A, Geusens P, Vandevyver C, Raus J, Stinissen P . 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 2000; 39: 1189–1201.

    Article  CAS  PubMed  Google Scholar 

  22. Jenkins RN, Nikaein A, Zimmermann A, Meek K, Lipsky PE . T cell receptor V beta gene bias in rheumatoid arthritis. J Clin Invest 1993; 92: 2688–2701.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Williams WV, Fang Q, Demarco D, VonFeldt J, Zurier RB, Weiner DB . Restricted heterogeneity of T cell receptor transcripts in rheumatoid synovium. J Clin Invest 1992; 90: 326–333.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Li Y, Sun GR, Tumang JR, Crow MK, Friedman SM . CDR3 sequence motifs shared by oligoclonal rheumatoid arthritis synovial T cells. Evidence for an antigen-driven response. J Clin Invest 1994; 94: 2525–2531.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Mima T, Ohshima S, Sasi M, Nishioka K, Shimizu M, Murata N . Dominant and shared T cell receptor beta chain variable regions of T cells inducing synovial hyperplasia in rheumatoid arthritis. Biochem Biophys Res Commun 1999; 263: 172–180.

    Article  CAS  PubMed  Google Scholar 

  26. Davey MP, Burgoine GA, Woody CN . TCRB clonotypes are present in CD4+ T cell populations prepared directly from rheumatoid arthritis. Hum Immunol 1997; 55: 11–21.

    Article  CAS  PubMed  Google Scholar 

  27. Even J, Lim A, Puisieux I, Ferradini L, Dietrich PY, Toubert A . T-cell repertoires in healthy and diseased human tissues analysed by T-cell receptor beta-chain CDR3 size determination: evidence for oligoclonal expansions in tumours and inflammatory diseases. Res Immunol 1995; 146: 65–80.

    Article  CAS  PubMed  Google Scholar 

  28. Wagner UG, Koetz K, Weyand CM, Goronzy JJ . Perturbation of the T cell repertoire in rheumatoid arthritis. Proc Natl Acad Sci USA 1998; 95: 14447–14452.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Cohen SE, Bodmer HC . Cytotoxic T lymphocytes recognize and lyse chondrocytes under inflammatory, but not non-inflammatory conditions. Immunology 2003; 109: 8–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Moreland LW, Heck Jr LW, Koopman WJ et al. V beta 17 T cell receptor peptide vaccination in rheumatoid arthritis: results of phase I dose escalation study. J Rheumatol 1996; 23: 1353–1362.

    CAS  PubMed  Google Scholar 

  31. Feldmann M, Brennan FM, Maini RN . Role of cytokines in rheumatoid arthritis. Annu Rev Immunol 1996; 14: 397–440.

    Article  CAS  PubMed  Google Scholar 

  32. Hong J, Zang YC, Tejada-Simon MV et al. A common TCR V-D-J sequence in V beta 13.1 T cells recognizing an immunodominant peptide of myelin basic protein in multiple sclerosis. J Immunol 1999; 163: 3530–3538.

    CAS  PubMed  Google Scholar 

  33. Moreland LW, Morgan EE, Adamson III TC et al. T cell receptor peptide vaccination in rheumatoid arthritis: a placebo-controlled trial using a combination of Vbeta3, Vbeta14, and Vbeta17 peptides. Arthritis Rheum 1998; 41: 1919–1929.

    Article  CAS  PubMed  Google Scholar 

  34. Tang J, Myracle AD, Allen S, Karita E, Musonda R, Fultz PN . Novel alleles at the lymphotoxin alpha (LTalpha) locus mark extended HLA haplotypes in native Africans. Hum Immunol 2001; 62: 269–278.

    Article  CAS  PubMed  Google Scholar 

  35. Oksenberg JR, Panzara MA, Begovich A et al. Selection for T-cell receptor V beta-D beta-J beta gene rearrangements with specificity for a myelin basic protein peptide in brain lesions of multiple sclerosis. Nature 1993; 362: 68–70.

    Article  CAS  PubMed  Google Scholar 

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Author notes

  1. W Sun and H Nie: These authors contributed equally to this work.

Authors and Affiliations

  1. Joint Immunology Laboratory, Health Science Center and Shanghai Institute of Immunology, Shanghai Institutes of Biological Sciences and Shanghai Second Medical University, Shanghai, China

    W Sun, H Nie, N Li, D Zhang & J Z Zhang

  2. E-Institute of Shanghai Universities, Shanghai, China

    W Sun, Y C Q Zang, S Prasad, R R Robinson & J Z Zhang

  3. Guanghua Rheumatology Hospital, Shanghai, China

    N Li & E Sercarz

  4. Hong Kong Chinese University, Hong Kong, China

    G Feng, L Ni & R Xu

  5. Baylor College of Medicine, Houston, TX, USA

    W Ho

  6. Torrey Pines Institute for Molecular Studies, San Diego, CA, USA

    J Z Zhang

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  1. W Sun
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Correspondence to J Z Zhang.

Additional information

The work was supported by grants from Chinese Academy of Sciences (Bai-ren Program and Grant KSCX2-SW-212), Chinese National Natural Science Foundation (Grant 30028020) and National Projects 863 (Grant 2002AA216121) and Research Grant 2002CCCD2000 of the Chinese Ministry of Science and Technology and by grants from MAXX Genetech.

Supplementary Information accompanies the paper on Genes and Immunity website (http://www.nature.com/Gene).

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Sun, W., Nie, H., Li, N. et al. Skewed T-cell receptor BV14 and BV16 expression and shared CDR3 sequence and common sequence motifs in synovial T cells of rheumatoid arthritis. Genes Immun 6, 248–261 (2005). https://doi.org/10.1038/sj.gene.6364166

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