Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1989 Jan;86(2):636–640. doi: 10.1073/pnas.86.2.636

Persistence of collagen type II-specific T-cell clones in the synovial membrane of a patient with rheumatoid arthritis.

M Londei 1, C M Savill 1, A Verhoef 1, F Brennan 1, Z A Leech 1, V Duance 1, R N Maini 1, M Feldmann 1
PMCID: PMC286527  PMID: 2463633

Abstract

Rheumatoid arthritis is an autoimmune disease characterized by T-cell infiltration of the synovium of joints. Analysis of the phenotype and antigen specificity of the infiltrating cells may thus provide insight into the pathogenesis of rheumatoid arthritis. T cells were cloned with interleukin 2, a procedure that selects for in vivo-activated cells. All clones had the CD4 CDW29 phenotype. Their antigen specificity was tested by using a panel of candidate joint autoantigens. Four of 17 reacted against autologous blood mononuclear cells. Two clones proliferated in response to collagen type II. After 21 months, another set of clones was derived from synovial tissue of the same joint. One of eight clones tested showed a strong proliferative response against collagen type II. The uncloned synovial T cells of a third operation from another joint also responded to collagen type II. The persistence of collagen type II-specific T cells in active rheumatoid joints over a period of 3 years suggests that collagen type II could be one of the autoantigens involved in perpetuating the inflammatory process in rheumatoid arthritis.

Full text

PDF
636

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bayliss M. T., Roughley P. J. The properties of proteoglycan prepared from human articular cartilage by using associative caesium chloride gradients of high and low starting densities. Biochem J. 1985 Nov 15;232(1):111–117. doi: 10.1042/bj2320111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bensussan A., Meuer S. C., Schlossman S. F., Reinherz E. L. Delineation of an immunoregulatory amplifier population recognizing autologous Ia molecules. Analysis with human T cell clones. J Exp Med. 1984 Feb 1;159(2):559–576. doi: 10.1084/jem.159.2.559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Boylston A. W., Borst J., Yssel H., Blanchard D., Spits H., de Vries J. E. Properties of a panel of monoclonal antibodies which react with the human T cell antigen receptor on the leukemic line HPB-ALL and a subset of normal peripheral blood T lymphocytes. J Immunol. 1986 Jul 15;137(2):741–744. [PubMed] [Google Scholar]
  4. Burmester G. R., Jahn B., Gramatzki M., Zacher J., Kalden J. R. Activated T cells in vivo and in vitro: divergence in expression of Tac and Ia antigens in the nonblastoid small T cells of inflammation and normal T cells activated in vitro. J Immunol. 1984 Sep;133(3):1230–1234. [PubMed] [Google Scholar]
  5. Emery P., Gentry K. C., Mackay I. R., Muirden K. D., Rowley M. Deficiency of the suppressor inducer subset of T lymphocytes in rheumatoid arthritis. Arthritis Rheum. 1987 Aug;30(8):849–856. doi: 10.1002/art.1780300802. [DOI] [PubMed] [Google Scholar]
  6. Fontana A., Hengartner H., Weber E., Fehr K., Grob P. J., Cohen G. Interleukin 1 activity in the synovial fluid of patients with rheumatoid arthritis. Rheumatol Int. 1982;2(2):49–53. doi: 10.1007/BF00541245. [DOI] [PubMed] [Google Scholar]
  7. Fox R., Sportsman R., Rhodes G., Luka J., Pearson G., Vaughan J. Rheumatoid arthritis synovial membrane contains a 62,000-molecular-weight protein that shares an antigenic epitope with the Epstein-Barr virus-encoded associated nuclear antigen. J Clin Invest. 1986 May;77(5):1539–1547. doi: 10.1172/JCI112469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Holoshitz J., Klajman A., Drucker I., Lapidot Z., Yaretzky A., Frenkel A., van Eden W., Cohen I. R. T lymphocytes of rheumatoid arthritis patients show augmented reactivity to a fraction of mycobacteria cross-reactive with cartilage. Lancet. 1986 Aug 9;2(8502):305–309. doi: 10.1016/s0140-6736(86)90003-6. [DOI] [PubMed] [Google Scholar]
  9. Janossy G., Panayi G., Duke O., Bofill M., Poulter L. W., Goldstein G. Rheumatoid arthritis: a disease of T-lymphocyte/macrophage immunoregulation. Lancet. 1981 Oct 17;2(8251):839–842. doi: 10.1016/s0140-6736(81)91107-7. [DOI] [PubMed] [Google Scholar]
  10. Klareskog L., Forsum U., Scheynius A., Kabelitz D., Wigzell H. Evidence in support of a self-perpetuating HLA-DR-dependent delayed-type cell reaction in rheumatoid arthritis. Proc Natl Acad Sci U S A. 1982 Jun;79(11):3632–3636. doi: 10.1073/pnas.79.11.3632. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Londei M., Bottazzo G. F., Feldmann M. Human T-cell clones from autoimmune thyroid glands: specific recognition of autologous thyroid cells. Science. 1985 Apr 5;228(4695):85–89. doi: 10.1126/science.3871967. [DOI] [PubMed] [Google Scholar]
  12. Londei M., Grubeck-Loebenstein B., de Berardinis P., Greenall C., Feldmann M. Efficient propagation and cloning of human T cells in the absence of antigen by means of OKT3, interleukin 2, and antigen-presenting cells. Scand J Immunol. 1988 Jan;27(1):35–46. doi: 10.1111/j.1365-3083.1988.tb02321.x. [DOI] [PubMed] [Google Scholar]
  13. Maini R. N., Plater-Zyberk C., Andrew E. Autoimmunity in rheumatoid arthritis. An approach via a study of B lymphocytes. Rheum Dis Clin North Am. 1987 Aug;13(2):319–338. [PubMed] [Google Scholar]
  14. Mason J. C., Venables P. J., Smith P. R., Maini R. N. Characterisation of non-histone nuclear proteins cross reactive with purified rheumatoid factors. Ann Rheum Dis. 1985 May;44(5):287–293. doi: 10.1136/ard.44.5.287. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Miller E. J., Harris E. D., Jr, Chung E., Finch J. E., Jr, McCroskery P. A., Butler W. T. Cleavage of Type II and III collagens with mammalian collagenase: site of cleavage and primary structure at the NH2-terminal portion of the smaller fragment released from both collagens. Biochemistry. 1976 Feb 24;15(4):787–792. doi: 10.1021/bi00649a009. [DOI] [PubMed] [Google Scholar]
  16. Pujol-Borrell R., Todd I., Doshi M., Bottazzo G. F., Sutton R., Gray D., Adolf G. R., Feldmann M. HLA class II induction in human islet cells by interferon-gamma plus tumour necrosis factor or lymphotoxin. Nature. 1987 Mar 19;326(6110):304–306. doi: 10.1038/326304a0. [DOI] [PubMed] [Google Scholar]
  17. Rhodes G., Carson D. A., Valbracht J., Houghten R., Vaughan J. H. Human immune responses to synthetic peptides from the Epstein-Barr nuclear antigen. J Immunol. 1985 Jan;134(1):211–216. [PubMed] [Google Scholar]
  18. Rock K. L., Benacerraf B. The role of Ia molecules in the activation of T lymphocytes. III. Antigen-specific, Ia-restricted, interleukin 2-producing T cell hybridomas with detectable affinity for the restricting I-A molecule. J Exp Med. 1983 Jan 1;157(1):359–364. doi: 10.1084/jem.157.1.359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Rowley M. J., Williamson D. J., Mackay I. R. Evidence for local synthesis of antibodies to denatured collagen in the synovium in rheumatoid arthritis. Arthritis Rheum. 1987 Dec;30(12):1420–1425. doi: 10.1002/art.1780301215. [DOI] [PubMed] [Google Scholar]
  20. Saklatvala J. Tumour necrosis factor alpha stimulates resorption and inhibits synthesis of proteoglycan in cartilage. Nature. 1986 Aug 7;322(6079):547–549. doi: 10.1038/322547a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Schlesier M., Ramb-Lindhauer C., Gärtner M., Peter H. H. Analysis of T-cell cultures and clones from a patient with classic rheumatoid arthritis--evidence for the existence of autoreactive T-cell clones in blood and synovial fluid. Rheumatol Int. 1984;4 (Suppl):1–9. doi: 10.1007/BF00541272. [DOI] [PubMed] [Google Scholar]
  22. Stuart J. M., Townes A. S., Kang A. H. Collagen autoimmune arthritis. Annu Rev Immunol. 1984;2:199–218. doi: 10.1146/annurev.iy.02.040184.001215. [DOI] [PubMed] [Google Scholar]
  23. Turner M., Londei M., Feldmann M. Human T cells from autoimmune and normal individuals can produce tumor necrosis factor. Eur J Immunol. 1987 Dec;17(12):1807–1814. doi: 10.1002/eji.1830171220. [DOI] [PubMed] [Google Scholar]
  24. Van Boxel J. A., Paget S. A. Predominantly T-cell infiltrate in rheumatoid synovial membranes. N Engl J Med. 1975 Sep 11;293(11):517–520. doi: 10.1056/NEJM197509112931101. [DOI] [PubMed] [Google Scholar]
  25. Yoo T. J., Kim S. Y., Stuart J. M., Floyd R. A., Olson G. A., Cremer M. A., Kang A. H. Induction of arthritis in monkeys by immunization with type II collagen. J Exp Med. 1988 Aug 1;168(2):777–782. doi: 10.1084/jem.168.2.777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Zvaifler N. J. The immunopathology of joint inflammation in rheumatoid arthritis. Adv Immunol. 1973;16(0):265–336. doi: 10.1016/s0065-2776(08)60299-0. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES