Skip to main content
PMC home page
Immunology logoLink to Immunology
. 1995 Jul;85(3):461–466.

Synovial fibroblasts as accessory cells for staphylococcal enterotoxin-mediated T-cell activation.

M Kraft 1, S Filsinger 1, K L Krämer 1, D Kabelitz 1, G M Hänsch 1, M Schoels 1
PMCID: PMC1383921  PMID: 7558136

Abstract

Rheumatoid arthritis (RA) is thought to be the result of T-cell-mediated autoimmune phenomena. So far, a critical autoantigen has not been identified. Recently, superantigens have been implied in the pathogenesis of RA. In the present study it was tested whether major histocompatibility complex (MHC) class II-positive synovial fibroblast cells (SFC) function as superantigen-presenting cells. SFC were stimulated with interferon-gamma (IFN-gamma) to express class II antigens; then they were cultivated in the presence of T cells with or without staphylococcal enterotoxins (SE). T-cell activation was measured as proliferation and interleukin-2 (IL-2) production. Depending on the dose and type of SE, activation of T-cell clones and also of peripheral T cells was seen. T-cell activation was inhibited by antibodies to MHC class II antigens and also by antibodies to intracellular adhesion molecule type-1 (ICAM-1). The data suggest that class II-positive SFC have the capacity to serve as accessory cells for superantigen-mediated T-cell activation. Thus SFC may participate in the propagation of a T-cell dependent immune response.

Full text

PDF

Selected References

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

  1. 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]
  2. Burmester G. R., Jahn B., Rohwer P., Zacher J., Winchester R. J., Kalden J. R. Differential expression of Ia antigens by rheumatoid synovial lining cells. J Clin Invest. 1987 Sep;80(3):595–604. doi: 10.1172/JCI113111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chin J. E., Winterrowd G. E., Krzesicki R. F., Sanders M. E. Role of cytokines in inflammatory synovitis. The coordinate regulation of intercellular adhesion molecule 1 and HLA class I and class II antigens in rheumatoid synovial fibroblasts. Arthritis Rheum. 1990 Dec;33(12):1776–1786. doi: 10.1002/art.1780331204. [DOI] [PubMed] [Google Scholar]
  4. Dayer J. M., Krane S. M., Russell R. G., Robinson D. R. Production of collagenase and prostaglandins by isolated adherent rheumatoid synovial cells. Proc Natl Acad Sci U S A. 1976 Mar;73(3):945–949. doi: 10.1073/pnas.73.3.945. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fischer H., Gjörloff A., Hedlund G., Hedman H., Lundgren E., Kalland T., Sjögren H. O., Dohlsten M. Stimulation of human naive and memory T helper cells with bacterial superantigen. Naive CD4+45RA+ T cells require a costimulatory signal mediated through the LFA-1/ICAM-1 pathway. J Immunol. 1992 Apr 1;148(7):1993–1998. [PubMed] [Google Scholar]
  6. Geppert T. D., Lipsky P. E. Antigen presentation by interferon-gamma-treated endothelial cells and fibroblasts: differential ability to function as antigen-presenting cells despite comparable Ia expression. J Immunol. 1985 Dec;135(6):3750–3762. [PubMed] [Google Scholar]
  7. Gregersen P. K., Silver J., Winchester R. J. The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum. 1987 Nov;30(11):1205–1213. doi: 10.1002/art.1780301102. [DOI] [PubMed] [Google Scholar]
  8. Harris E. D., Jr Rheumatoid arthritis. Pathophysiology and implications for therapy. N Engl J Med. 1990 May 3;322(18):1277–1289. doi: 10.1056/NEJM199005033221805. [DOI] [PubMed] [Google Scholar]
  9. Hazenberg M. P., Klasen I. S., Kool J., Ruseler-van Embden J. G., Severijnen A. J. Are intestinal bacteria involved in the etiology of rheumatoid arthritis? Review article. APMIS. 1992 Jan;100(1):1–9. doi: 10.1111/j.1699-0463.1992.tb00833.x. [DOI] [PubMed] [Google Scholar]
  10. Herman A., Kappler J. W., Marrack P., Pullen A. M. Superantigens: mechanism of T-cell stimulation and role in immune responses. Annu Rev Immunol. 1991;9:745–772. doi: 10.1146/annurev.iy.09.040191.003525. [DOI] [PubMed] [Google Scholar]
  11. Herrmann T., Romero P., Sartoris S., Paiola F., Accolla R. S., Maryanski J. L., MacDonald H. R. Staphylococcal enterotoxin-dependent lysis of MHC class II negative target cells by cytolytic T lymphocytes. J Immunol. 1991 Apr 15;146(8):2504–2512. [PubMed] [Google Scholar]
  12. Holoshitz J., Matitiau A., Cohen I. R. Arthritis induced in rats by cloned T lymphocytes responsive to mycobacteria but not to collagen type II. J Clin Invest. 1984 Jan;73(1):211–215. doi: 10.1172/JCI111193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Howell M. D., Diveley J. P., Lundeen K. A., Esty A., Winters S. T., Carlo D. J., Brostoff S. W. Limited T-cell receptor beta-chain heterogeneity among interleukin 2 receptor-positive synovial T cells suggests a role for superantigen in rheumatoid arthritis. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10921–10925. doi: 10.1073/pnas.88.23.10921. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kabelitz D., Wesselborg S. Life and death of a superantigen-reactive human CD4+ T cell clone: staphylococcal enterotoxins induce death by apoptosis but simultaneously trigger a proliferative response in the presence of HLA-DR+ antigen-presenting cells. Int Immunol. 1992 Dec;4(12):1381–1388. doi: 10.1093/intimm/4.12.1381. [DOI] [PubMed] [Google Scholar]
  15. Keystone E. C., Minden M., Klock R., Poplonski L., Zalcberg J., Takadera T., Mak T. W. Structure of T cell antigen receptor beta chain in synovial fluid cells from patients with rheumatoid arthritis. Arthritis Rheum. 1988 Dec;31(12):1555–1557. doi: 10.1002/art.1780311213. [DOI] [PubMed] [Google Scholar]
  16. Koning F., Rust C. Staphylococcal enterotoxin-mediated human T-T cell interactions. J Immunol. 1992 Jul 1;149(1):317–322. [PubMed] [Google Scholar]
  17. Lindblad S., Klareskog L., Hedfors E., Forsum U., Sundström C. Phenotypic characterization of synovial tissue cells in situ in different types of synovitis. Arthritis Rheum. 1983 Nov;26(11):1321–1332. doi: 10.1002/art.1780261104. [DOI] [PubMed] [Google Scholar]
  18. McCulloch J., Lydyard P. M., Rook G. A. Rheumatoid arthritis: how well do the theories fit the evidence? Clin Exp Immunol. 1993 Apr;92(1):1–6. doi: 10.1111/j.1365-2249.1993.tb05938.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Miltenburg A. M., van Laar J. M., Daha M. R., de Vries R. R., van den Elsen P. J., Breedveld F. C. Dominant T-cell receptor beta-chain gene rearrangements indicate clonal expansion in the rheumatoid joint. Scand J Immunol. 1990 Jan;31(1):121–126. doi: 10.1111/j.1365-3083.1990.tb02750.x. [DOI] [PubMed] [Google Scholar]
  20. Nickoloff B. J., Mitra R. S., Green J., Zheng X. G., Shimizu Y., Thompson C., Turka L. A. Accessory cell function of keratinocytes for superantigens. Dependence on lymphocyte function-associated antigen-1/intercellular adhesion molecule-1 interaction. J Immunol. 1993 Mar 15;150(6):2148–2159. [PubMed] [Google Scholar]
  21. Stamenkovic I., Stegagno M., Wright K. A., Krane S. M., Amento E. P., Colvin R. B., Duquesnoy R. J., Kurnick J. T. Clonal dominance among T-lymphocyte infiltrates in arthritis. Proc Natl Acad Sci U S A. 1988 Feb;85(4):1179–1183. doi: 10.1073/pnas.85.4.1179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Todd J. A., Acha-Orbea H., Bell J. I., Chao N., Fronek Z., Jacob C. O., McDermott M., Sinha A. A., Timmerman L., Steinman L. A molecular basis for MHC class II--associated autoimmunity. Science. 1988 May 20;240(4855):1003–1009. doi: 10.1126/science.3368786. [DOI] [PubMed] [Google Scholar]
  23. Uchiyama T., Araake M., Yan X. J., Miyanaga Y., Igarashi H. Involvement of HLA class II molecules in acquisition of staphylococcal enterotoxin A-binding activity and accessory cell activity in activation of human T cells by related toxins in vascular endothelial cells. Clin Exp Immunol. 1992 Feb;87(2):322–328. doi: 10.1111/j.1365-2249.1992.tb02995.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Uematsu Y., Wege H., Straus A., Ott M., Bannwarth W., Lanchbury J., Panayi G., Steinmetz M. The T-cell-receptor repertoire in the synovial fluid of a patient with rheumatoid arthritis is polyclonal. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8534–8538. doi: 10.1073/pnas.88.19.8534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. von Kempis J., Torbohm I., Schönermark M., Jahn B., Seitz M., Hänsch G. M. Effect of the late complement components C5b-9 and of platelet-derived growth factor on the prostaglandin release of human synovial fibroblast-like cells. Int Arch Allergy Appl Immunol. 1989;90(3):248–255. doi: 10.1159/000235032. [DOI] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES