Rheumatology International

, Volume 10, Issue 5, pp 203–210 | Cite as

Stimulation of rheumatoid synovial and blood T cells and lines by synovial fluid and interleukin-2: Characterization of clones and recognition of a co-stimulatory effect

  • N. Hain
  • S. Alsalameh
  • W. M. Bertling
  • J. R. Kalden
  • G. R. Burmester
Article
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Accepted:

Summary

Rheumatoid arthritis (RA) is characterized by the presence of interleukin-2 (Il-2) receptor-positive T cells in the peripheral blood and synovial compartments. Utilizing the limiting dilution technique, the precursor frequencies of Il-2 responsive T cells were determined in peripheral blood and synovial sites from RA patients and in the blood of normal donors. The frequencies of Il-2 responsive T cells were significantly higher in RA patients (range from 1/180 to 1/7432) compared to normal donors (range from 1/400 to 1/8163). T-cell clones raised by the addition of Il-2 alone were predominantly of the CD4-positive phenotype. Peripheral blood T cells, synovial T-cell clones and lines derived from RA patients were co-stimulated with Il-2 and synovial fluid or supernatants from cultured synovial lining cells. This co-stimulation induced a strikingly enhanced proliferative T-cell response while synovial fluid alone was without effect. This stimulatory activity was found in the high molecular weight range (approximately 150 kDa) and could not be attributed to the action of immunoglobulins or known cytokines such as Il-2 or interleukin-1 (Il-1), suggesting the activity of a material that modulates the Il-2-dependent growth of T cells. The co-stimulatory capacity of synovial fluid with Il-2 may be relevant to the activated state, especially of synovial T cells.

Key words

Rheumatoid arthritis Synovial fluid Interleukin-2 Synovial T cells Co-stimulatory effect 
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References

  1. 1.
    Yu DTY, Winchester RJ, Fu SM, Gibofsky A, Ko HS, Kunkel HG (1980) Peripheral blood Ia positive T cells: increase in certain diseases and after immunisation. J Exp Med 151: 91–100CrossRefPubMedGoogle Scholar
  2. 2.
    Burmester GR, Yu DTY, Irani A-M, Kunkel HG, Winchester RJ (1981) Ia+ T cells in synovial fluid and tissues of patients with rheumatoid arthritis. Arthritis Rheum 24: 1370–1376PubMedGoogle Scholar
  3. 3.
    Burmester GR, Jahn B, Gramatzki M, Zacher J, Kalden JR (1984) 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 133: 1230–1235PubMedGoogle Scholar
  4. 4.
    Wilkins JA, Olivier SL, Warrington RJ (1984) Generation of interleukin-2-dependent T cell lines from synovial fluids in rheumatoid arthritis. Clin Exp Immunol 58: 1–6PubMedGoogle Scholar
  5. 5.
    Ofosu-Appiah WA, McKenna RM, Warrington RJ, Wilkins JA (1986) Characterization of Il-2 responsive synovial T lymphocytes in rheumatoid arthritis. I. Production of Il-2 dependent T cell clones from synovial fluid in peripheral blood. Clin Exp Immunol 64: 555–562PubMedGoogle Scholar
  6. 6.
    Stratton JA, Peter JB (1978) The response of peripheral blood and synovial fluid lymphocytes of patients with rheumatoid arthritis due to in vitro stimulation with mitogen. Clin Immunol Immunopathol 10: 233–241CrossRefPubMedGoogle Scholar
  7. 7.
    Corrigall V, Panayi GS, Laulent R (1979) Lymphocytes studies in rheumatoid arthritis. III. A comparative study of the response of peripheral blood and synovial fluid lymphocytes to phytomitogen. Scand J Rheumatol 8: 10–16PubMedGoogle Scholar
  8. 8.
    Burmester GR, Kalden JR, Peter HH, Schede I, Beck D, Witenborg A (1978) Immunological and functional characteristics of peripheral blood and synovial fluid lymphocytes from patients with rheumatoid arthritis. Scand J Immunol 7: 405–411PubMedGoogle Scholar
  9. 9.
    Jahn B, Burmester GR, Stock P, Rohwer P, Kalden JR (1987) Functional and phenotypical characterization of activated T cells from intra-articular sites in inflammatory joint diseases. Possible modulation of the CD3 antigen. Scand J Immunol 26: 745–754PubMedGoogle Scholar
  10. 10.
    Wood DD, Ihrie EJ, Hamerman D (1985) Release of Interleukin-1 from human synovial tissue in vitro. Arthritis Rheum 28: 853–862PubMedGoogle Scholar
  11. 11.
    Nouri AME, Panayi GS, Goodman SM (1984) Cytokines and the chronic inflammation of rheumatic diseases. I. The presence of interleukin-1 in synovial fluids. Clin Exp Immunol 55: 295–302PubMedGoogle Scholar
  12. 12.
    Nouri AME, Panayi GS, Goodman SM (1984) Cytokines and the chronic inflammation of rheumatic diseases. II. The presence of interleukin-2 in synovial fluids. Clin Exp Immunol 58: 402–409PubMedGoogle Scholar
  13. 13.
    Warrington RJ, Wilkins JA (1983) Synovial T lymphocytes in rheumatoid arthritis. J Rheumatol 11: 93–96Google Scholar
  14. 14.
    Fontana A, Hengartner H, Weber E, Fehr K, Gorb PJ, Cohen G (1982) Interleukin-1 activity in the synovial fluid of patients with rheumatoid arthritis. Rheumatol Int 2: 49–53CrossRefPubMedGoogle Scholar
  15. 15.
    Wood DD, Ihrie EJ, Dinarello CA, Cohen PL (1983) Isolation of an interleukin-1-like factor from human joint effusions. Arthritis Rheum 26: 975–982PubMedGoogle Scholar
  16. 16.
    Egerland T, Lund H (1987) Immunoregulatory lymphokines in rheumatoid joint. I. Search for interleukin-2 in synovial fluid. Scand J Immunol 25: 101–106PubMedGoogle Scholar
  17. 17.
    Miossec P, Kashiwado T, Ziff M (1987) Inhibitor of Interleukin-2 in rheumatoid synovial fluid. Arthritis Rheum 30: 121–129PubMedGoogle Scholar
  18. 18.
    Kashiwado T, Miossec P, Oppenheimer-Marks N, Ziff M (1987) Inhibitor of Interleukin-2 synthesis and response in rheumatoid synovial fluid. Arthritis Rheum 30: 1339–1347PubMedGoogle Scholar
  19. 19.
    Emery P, Gentry KC, Kelso A, Mackay IR (1988) Interleukin-2 inhibitor in synovial fluid. Clin Exp Immunol 72: 60–66PubMedGoogle Scholar
  20. 20.
    Smith MD, Haynes DR, Roberts-Thromson PJ (1989) Interleukin-2 and interleukin-2 inhibitors in human serum and synovial fluid. I. Characterization of the inhibitors and its mechanism of action. J Rheumatol 16: 149–157PubMedGoogle Scholar
  21. 21.
    Anastassiades T, Robertson W (1984) Modulation of mitogen-dependent lymphocyte stimulation by hyaluronic acid. J Rheumatol 11: 729–735PubMedGoogle Scholar
  22. 22.
    Goldberg RL, Toole BP (1987) Hyaluronate inhibition of cell proliferation. Arthritis Rheum 30: 769–778PubMedGoogle Scholar
  23. 23.
    Hain N, Burmester GR, Kalden JR (1988) T cell clones in rheumatoid arthritis (RA). Scand J Rheumatol [Suppl] 76: 145–152Google Scholar
  24. 24.
    Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, Medsger TA, Mitchell DM, Neustadt DH, Pinals RS, Schaller JG, Sharp JT, Wilder RL, Hunder GG (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31: 315–324PubMedGoogle Scholar
  25. 25.
    Fleischer B (1982) Cloned lines of human cytotoxic T lymphocytes with specificity for influenza virus. J Immunol 129: 1731–1735PubMedGoogle Scholar
  26. 26.
    Szer IS, Irani A, Burmester GR, Winchester RJ (1984) Four new surface antigen of T lymphocytes. First International Workshop on Human Leukocytes Differentiation Antigens, ParisGoogle Scholar
  27. 27.
    Reinherz EL, Kung PC, Goldstein G, Schlossmann SF (1980) A monoclonal antibody reactive with the human cytotoxic/suppressor cell subset previously defined by a heteroantiserum termed TH2. J Immunol 124: 1301–1307PubMedGoogle Scholar
  28. 28.
    Uchiyama T, Broder S, Waldmann TA (1981) A monoclonal antibody (anti-Tac) reactive with activated and functional mature human T cells. I. Production of anti-Tac monoclonal antibody and distribution of Tac(+) cells. J Immunol 126: 1393–1401PubMedGoogle Scholar
  29. 29.
    Lefkovits I, Waldmann H (1979) Limiting dilution analysis of cells in the immune system. Cambridge University Press, CambridgeGoogle Scholar
  30. 30.
    Ofosu-Appiah WA, Warrington RJ, Wilkins JA (1987) Characterization of Il-2 resposive synovial T lymphocytes in rheumatoid arthritis. II. Functional properties. Rheumatol Int 7: 147–151CrossRefPubMedGoogle Scholar
  31. 31.
    Vie H, Bonneville M, Sondermeyer P, Moreau JF, Soulillou JP (1986) Limiting dilution analysis (LDA) of cells responding to recombinant interleukin-2 without previous stimulation: evidence that all responding cells are lymphokine potent effectors. Immunology 57: 2735–2739Google Scholar
  32. 32.
    Schlesier M, Haas G, Wolff-Vorbeck G, Melchers I, Peter HH (1989) Autoreactive T cells in rheumatic diseases. 1. Analysis of growth frequencies and autoreactivity of T cells in patients with rheumatoid arthritis and lyme disease. J Autoimmun 2: 31–49CrossRefPubMedGoogle Scholar
  33. 33.
    Smith KA, Cantrell DA (1985) Interleukin-2 regulates its own receptor. Proc Natl Acad Sci USA 82: 864–868PubMedGoogle Scholar
  34. 34.
    Robb RJ, Greene WC, Rusk CM (1984) Low and high affinity cellular receptors for interleukin-2: implications for the level of TAC antigen. J Exp Med 160: 1126–1146CrossRefPubMedGoogle Scholar
  35. 35.
    Crout JE, McDuffie FC, Ritts RE Jr (1976) Induction of peripheral blood lymphocytes transformation by autologous synovial fluid lymphocytes and synovial fluid. Arthritis Rheum 19: 523–531PubMedGoogle Scholar
  36. 36.
    Alsalameh S, Jahn B, Krause A, Kalden JR, Burmester GR (1990) Antigenicity and accessory cell function of human articular chondrocytes. J Rheumatol (in press)Google Scholar
  37. 37.
    Alsalameh S, Mollenhauer J, Hain N, Stock KP, Kalden JR, Burmester GR (1990) Cellular immune response towards human articular chondrocytes. II. T cell reactivity against chondrocytes and fibroblast membranes in destructive joint diseases. Arthritis Rheum (in press)Google Scholar
  38. 38.
    Saxne T, Heinegard D, Wollheim FA (1987) Cartilage proteoglycans in synovial fluid and serum in patients with inflammatory joint disease. Relation to systemic treatment. Arthritis Rheum 9: 972–977Google Scholar
  39. 39.
    Jasin HE (1985) Autoantibody specificities of immune complexes sequestered in articular cartilage of patients with rheumatoid arthritis and osteoarthritis. Arthritis Rheum 28: 241–248PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • N. Hain
    • 1
    • 2
  • S. Alsalameh
    • 1
    • 2
  • W. M. Bertling
    • 1
    • 2
  • J. R. Kalden
    • 1
    • 2
  • G. R. Burmester
    • 1
    • 2
  1. 1.Institute of Clinical Immunology and Rheumatology, Department of Medicine IIIUniversity of Erlangen-NürnbergErlangenGermany
  2. 2.Max-Planck Society, Clinical Research Unit for Rheumatology, Department of Medicine IIIUniversity of Erlangen-NürnbergErlangenGermany

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