Rheumatology International

, Volume 1, Issue 3, pp 139–143 | Cite as

Induction of a lymphotoxin-like mediator in peripheral blood and synovial fluid lymphocytes by incubation with synovial fluid from patients with rheumatoid arthritis

  • G. R. Burmester
  • P. Beck
  • R. Eife
  • H. H. Peter
  • J. R. Kalden
Short Communications


A significantly increased spontaneous cell-mediated cytotoxicity (SCMC) has been reported in synovial fluid lymphocytes (SFL) as compared to peripheral blood lymphocytes (PBL) of patients with rheumatoid arthritis (RA) and that of normal controls [1–3]. To determine whether this increased SCMC activity is due to the production of a lymphokine and related to the production of a lymphotoxin (LT)-like mediator, PBL from normal controls and PBL and SFL from RA patients were incubated either with a human melanoma cell line (IGR 3) or with cell-free synovial fluid (SF) from RA patients. The SF and the cell-free supernatants of the different cultures were tested for LT activity by estimation of inhibition of DNA synthesis of HeLa cell monolayers and they were added to a SCMC assay system using normal PBL and IGR 3 as target.

In the supernatants from cocultures of either PBL from controls or PBL and SFL from RA patients with IGR 3 cells, there was no significant difference in LT activity. An LT-like mediator was observed in the supernatants of all lymphocytes cocultured with SF, whereas SF alone and supernatants of lymphocytes alone exhibited little or no LT activity. In a control experiment, LT induction was not observed when normal lymphocytes were cultured with the serum of RA patients. Absorption of the culture supernatants with an insolubilised goat anti-human Ig did not remove LT activity. The demonstrated release of an LT-like mediator from lymphocytes incubated with SF might be one contributing mechanism to the inflammatory joint reaction in RA patients.

Key words

Rheumatoid arthritis Synovial fluid lymphocytes SCMC-activity Lymphotoxin 


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  1. 1.
    Burmester GR, Kalden JR, Peter HH, Schedel I, Beck P, Wittenborg A (1978) Immunological and functional characteristics of peripheral blood and synovial fluid lymphocytes from patients with rheumatoid arthritis. Scand J Immunol 7:405–417Google Scholar
  2. 2.
    MacLennan ICM, Loewi G (1970) The cytotoxic activity of mononuclear cells from joint fluid. Clin Exp Immunol 6:713–718Google Scholar
  3. 3.
    Corrigal VM, Panayi GS (1978) Lymphocyte studies in rheumatoid arthritis. II. Antibody-mediated and mitogen-induced lymphocyte cytotoxicity in synovial fluid and peripheral blood. Ann Rheum Dis 37:410–415Google Scholar
  4. 4.
    Peter HH, Eife RF, Kalden JR (1976) Spontaneous cytotoxicity (SCMC) of normal human lymphocytes against a human melanoma cell line: a phenomenon due to a lymphotoxin-like mediator. J Immunol 116:342–348Google Scholar
  5. 5.
    Sebök J, Talerman A, Wouters HW, Lems PH (1977) The activating effect of synovial fluid and washings of synovial membrane on autologous lymphocytes in rheumatoid arthritis. Arthritis Rheum 20:1350–1353Google Scholar
  6. 6.
    Stastny P, Rosenthal M, Andreis M, Ziff M (1975) Lymphokines in the rheumatoid joint. Arthritis Rheum 18:237–243Google Scholar
  7. 7.
    Maini RN, Horsfall A, Roffe L (1979) Lymphokines and rheumatoid arthritis. In: Panayi GS, Johnson PM (eds) Immunopathogenesis of rheumatoid arthritis. Reedbooks, Chertsey, pp 37–41Google Scholar
  8. 8.
    Kinsella TD (1973) Induction of autologous lymphocyte transformation by synovial fluid from patients with rheumatoid arthritis. Clin Exp Immunol 14:187–191Google Scholar
  9. 9.
    Eife RF, Eife G, August CS, Kuhre WL, Staehr-Johansen K (1974) Lymphotoxin production and blast cell transformation by cord blood lymphocytes: dissociated lymphocyte function in newborn infants. Cell Immunol 14:435–442Google Scholar
  10. 10.
    Kalden JR, Peter HH, Roubin R, Cesarini JP (1977) Human peripheral null-lymphocytes. I. Isolation, immunological and functional characterization. Eur J Immunol 7:537–543Google Scholar
  11. 11.
    David JR, David RA (1972) Cellular hypersensitivity and immunity. Prog Allergy 16:300–449Google Scholar
  12. 12.
    Granger GA (1970) Mechanism of lymphocytes-induced cell and tissue destruction in vitro. Am J Pathol 60:469–882Google Scholar
  13. 13.
    Eife RJ, August CS (1973) Detection of Lymphotoxin produced in mixed lymphocyte cultures (MLC): Variation in target cell sensitivity. Cell Immunol 9:163–168Google Scholar
  14. 14.
    Rocklin RE, Reardon G, Sheffer A, Churchill WH, David JR (1970) Proceedings of the Fifth Leukocyte Culture Conference. Harris J (ed). Appleton-Century-Crofts, New York, p 639Google Scholar
  15. 15.
    Evans R (1974) Specific and non-specific activation of macrophages. In: Wagner WH, Hahn H (eds) Activation of macrophages. Elsevier Excerpta Medica, Amsterdam New York, pp 305–314Google Scholar
  16. 16.
    Fischer H, Lohmann-Matthes ML, Ritter J (1974) The amplification of specific macrophage cytotoxicity by non-specific stimulants. In: Wagner WH, Hahn H (eds) Activation of macrophages. Elsevier Excerpta Medica, Amsterdam New York, pp 318–322Google Scholar

Copyright information

© Springer-Verlag 1981

Authors and Affiliations

  • G. R. Burmester
    • 1
  • P. Beck
    • 1
  • R. Eife
    • 2
  • H. H. Peter
    • 1
  • J. R. Kalden
    • 3
  1. 1.Division of Clinical Immunology and Blood Transfusion, Department of Internal MedicineMedical School of HannoverHannoverGermany
  2. 2.Department of PediatricsUniversity of MunichMunichGermany
  3. 3.Institut für klinische Immunologie und RheumatologieUniversität Erlangen-NürnbergErlangenGermany

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