Bacterial Heat-Shock Proteins and Autoimmune Disease

  • W. Van Eden
  • S. M. Anderton
  • A. B. J. Prakken
  • R. Van Der Zee
Part of the Infectious Agents and Pathogenesis book series (IAPA)


Of all the microorganisms, bacteria, especially, seem to exert continuous pressure on the immune system. The epithelial surfaces of the skin and the intestinal tract are colonized by a wide variety of bacterial species, forcing the immune system into a situation where it has to scan continuously an immense repertoire of foreign antigenic determinants. It may be self-evident that as much as the healthy immune system does not develop an aggressive response directed against self antigens, or autoantigens, the same immune system is not tuned to mount continuous and aggressive responses to antigens present in the resident bacterial flora. Nonetheless, the capacity to respond must be there. Within every healthy immune system, cells specific for autoantigens are present, and their potential for causing disease has been demonstrated in a variety of experimental autoimmune disease models. The mechanisms by which the immune


Peripheral Tolerance Bacterial Antigen Juvenile Chronic Arthritis Autoimmune Arthritis Human Hsp60 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Cohen, I. R., 1986, Regulation of autoimmune disease: Physiological and therapeutic, Immunol.Google Scholar
  2. 2.
    Toivanen, A., and Toivanen, P., 1991, Reactive vs. rheumatoid arthritis: What is to be learned?, in: Trends in Rheumatoid Arthritis Research( P. Hedquist,J. R. Kalden, R. Miiller-Peddinghaus and D. R. Robinson, eds.), Eular Publishers, Basel, Switzerland, pp. 29–35.Google Scholar
  3. 3.
    Whitehouse, D. J., Whitehouse, M. W., and Pearson, C. M., 1969, Passive transfer of adjuvant induced arthritis and allergic encephalomyelitis in rats using thoracic duct lymphocytes, Nature 224: 1322 - 1324.PubMedCrossRefGoogle Scholar
  4. 4.
    Holoshitz, J., Naparstek, Y, Ben-Nun, A., and Cohen, I. R., 1983, Lines of T lymphocytes induce or vaccinate against autoimmune arthritis, S dence 219: 56 - 58.CrossRefGoogle Scholar
  5. 5.
    Klasen, I. S., KoolJ., Melief, M. J., and Hazenberg, M., 1992, Arthritis autoreactive T cell lines obtained from rats after injection of intestinal bacterial cell wall fragments, Cell Immunol. 139: 455 - 467.Google Scholar
  6. 6.
    Cohen, I. R., 1992, The cognitive paradigm and the immunological homunculus, I mmunol . Today 13: 490 - 494.PubMedCrossRefGoogle Scholar
  7. 7.
    Hammerling, G.J., Schonrich, G., Ferber, I., and Arnold, B., 1993, Peripheral tolerance as a multi-step mechanism, Immunol. Rev. 133: 93 - 103.PubMedCrossRefGoogle Scholar
  8. 8.
    Kohashi, O., Kohashi, Y, Ozawa, A., and Shigematsu, N., 1986, Suppressive effect of E. colion adjuvant-induced arthritis in germ-free rats, Arthritis Rheum. 29: 547 - 552.PubMedCrossRefGoogle Scholar
  9. 9.
    Thompson, S. J., and Elson, C. J., 1993, Susceptibility to pristane-induced arthritis is altered with changes in bowel flora, Immunol. Lett. 36: 227 - 230.PubMedCrossRefGoogle Scholar
  10. 10.
    Bowman, M. A., Leiter, E. H., and Atkinson, M. A., 1994, Prevention of diabetes in the NOD mouse: Implications for therapeutic intervention in human disease, Immunol. Today 15: 115 - 120.PubMedCrossRefGoogle Scholar
  11. 11.
    Sadelain, M. W. J., Qin, H. Y, Sumoski, W., Parfrey, N., Singh, B., and Rabinovitch, A., 1990, Prevention of diabetes in the BB rat by early immunotherapy using Freund’s adjuvant,J. Autoimmun. 3: 671–680.PubMedCrossRefGoogle Scholar
  12. 12.
    Shehadh, N., Calcinaro, F., Bradley, B.J., Brucklim, I., Vardi, P., and Lafferty, KJ., 1994, Effect of adjuvant therapy on development of diabetes in mouse and man, Lancet 343: 706–707.CrossRefGoogle Scholar
  13. 13.
    Van Eden, W., Thole, J. E. R., van der Zee, R., Noordzij, A., van Embden, J. D. A., Hensen, E. J., and Cohen, I. R., 1988, Cloning of the mycobacterial epitope recognized by T lymphocytes in adjuvant arthritis, Nature 331: 171–173.PubMedCrossRefGoogle Scholar
  14. 14.
    Van Eden, W., Hogervorst, E. J., Hensen, E.J., van der Zee, R., van Embden,J. D. A., and Cohen, I. R., 1989, A cartilage-mimicking T cell epitope on a 65K mycobacterial heat shock protein: Adjuvant arthritis as a model for human rheumatoid arthritis, Curr. Top. Microbiol. Immunol. 145: 27–43.Google Scholar
  15. 15.
    Van Eden, W., 1991, Heat-shock proteins and the immune system, Immunol. Rev. 121: 5–28.PubMedCrossRefGoogle Scholar
  16. 16.
    Welch, W. J., 1993, How cells respond to stress, Sä. Am. 268: 56–62.CrossRefGoogle Scholar
  17. 17.
    Boog, C.J. P., de Graeff-Meeder, E. R., Lucassen, M. A., van der Zee, R., Voorhorst-Ogink, M. M., van Kooten, P.J. S., Geuze, H.J., and van Eden, W., 1992, Two monoclonal antibodies generated against human hsp60 show reactivity with synovial membranes of patients with juvenile chronic arthritis, J. Exp. Med. 175: 1805–1810.PubMedCrossRefGoogle Scholar
  18. 18.
    Anderton, S. M., van der Zee, R., Noordzij, A., and van Eden, W., 1994, Differential mycobacterial 65-kDa hsp T cell epitope recognition after AA inducing or protective immunization protocols,J. Immunol. 152: 3656.PubMedGoogle Scholar
  19. 19.
    Anderton, S. M., and W. van Eden, 1996, T lymphocyte recognition of hsp60 in experimental arthritis, in: Stress Proteins in Mediane (W. can Eden and D. Young, eds.), Marcel Dekker, New York, pp. 73–92.Google Scholar
  20. 20.
    Res, R C. M., Telgt, D., Laar, J. M., Oudkerk Pool, M., Breedveld, E C, and de Vries, R. R. P., 1990, Increased antigen reactivity of mononuclear cells from sites of chronic inflammation, Lancet 336: 1406–1408.PubMedCrossRefGoogle Scholar
  21. 21.
    Wilbrink, B., Holewijn, M., Bijlsma, J. W. J., van Roy, J. L. A. M., den Otter, W., and van Eden, W., 1993, Suppression of human cartilage proteoglycan synthesis by rheumatoid synovial fluid mononuclear cells activated with mycobacterial 60 kD heat-shock protein, Arthritis Rheum. 36: 514 - 518.Google Scholar
  22. 22.
    de Graeff-Meeder, E. R., van der Zee, R., Rijkers, G. X, Schuurman, H. J., Kuis, W., Bijlsma, J. W. J., Zegers, B.J. M., and van Eden, W., 1991, Recognition of human 60 kD heat shock protein by mononuclear cells from patients with juvenile chronic arthritis, Lancet 337: 1368 - 1372.PubMedCrossRefGoogle Scholar
  23. 23.
    . deGraeff-Meeder, E. R., van Eden, W., Rijkers, G. T., Kuis, W., Voorhorst-Ogink, M. M., van der Zee, R., Schuurman, H.-J., Helders, P. J. M., and Zegers, B. J. M., Juvenile chronic arthritis: T-cell reactivity to human hsp60 in patients with a favorable course of arthritis, J. Clin. Invest. 95:934-940.Google Scholar
  24. 24.
    Rosenthal, M., Bahous, L, and Ambrosini, G., 1991, Long term treatment of rheumatoid arthritis with OM-8980. A retrospective study, J. Rheum. 18: 1790 - 1793.PubMedGoogle Scholar
  25. 25.
    Vischer, T. L., 1988, A double blind multi center study of OM-8980 and auranofin in rheumatoid arthritis, Ann. Rheum. Dis. 47: 582 - 587.Google Scholar
  26. 26.
    Evavold, B. D., Sloan-Lancaster, J., and Allen, P. H., 1993, Tickling the TcR selective T-cell functions stimulated by altered peptide ligands, Immunol. Today 14: 602 - 609.PubMedCrossRefGoogle Scholar
  27. 27.
    Van Eden, W., Wauben, M. H. M., Boog, C.J. P., and van der Zee, R., 1993, Inhibition of autoimmune T cells by “competitor modulator” peptides, in: Progress in Immunology( J. Gergely, ed.), Springer Verlag, Budapest, pp. 587 - 594.Google Scholar
  28. 28.
    Wauben, M. H. M., Boog, C.J. P., van der Zee, R.,Joosten, L, Schlief, A., and van Eden, W., 1992, Disease inhibition by MHC binding peptide analogues of disease associated epitopes: More than blocking alone, J. Exp. Med. 176: 667 - 677.Google Scholar

Copyright information

© Plenum Press, New York 1996

Authors and Affiliations

  • W. Van Eden
    • 1
  • S. M. Anderton
    • 1
  • A. B. J. Prakken
    • 1
  • R. Van Der Zee
    • 1
  1. 1.Department of Immunology, Institute of Infectious Diseases and Immunology, Faculty of Veterinary MedicineUniversity of UtrechtUtrechtThe Netherlands

Personalised recommendations