Skip to main content
SpringerLink
Log in

Monoclonal antibodies and arthritis

  • Arthritis and Immunotherapy
  • Published:
Agents and Actions Aims and scope Submit manuscript

Abstract

Monoclonal antibodies to certain cell surface constituents on lymphocytes, monocytes and macrophages have been administered to Lewis rats with developing, established or adoptively transferred arthritis, to determine any immunomodulatory properties. Anti-CD4 antibodies against helper T-lymphocytes produced a dose related inhibition of developing arthritis; high dose levels completely suppressed all symptoms of arthritis and these rats were resistant to further attempts to induce arthritis. Anti-Ia (MHCII) antibodies also inhibited arthritis in a dose related manner; anti-pan T antibodies delayed the onset of arthritis, but antibodies against CD8 and IL-2 receptor positive cells were without effect. Development of type II collagen-induced arthritis was also inhibited by anti-CD4 treatment. Established arthritis could be temporatily inhibited by anti-CD4 antibodies, but rebound of arthritis invariably occurred after stopping treatment, as is the case with cyclosporin A. Similar results with anti-CD4 antibodies were obtained during treatment of arthritis adoptively transferred by arthritogenic T-lymphocytes. From these experiments it is clear that CD4 positive T-lymphocytes have a major role in the induction of adjuvant arthritis and that interaction between CD4 and Ia bearing cells is important. The rebound of arthritis that occurred after withdrawal of anti-CD4 treatment during established disease infers that cells in addition to helper T-lymphocytes are involved in the chronicity of arthritis, but these remain to be elucidated. These findings are discussed in relation to results with monoclonal antibodies in other models of arthritis and human rheumatoid arthritis; the prospects for human therapy are also discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. G. Janossy, O. Duke, L. W. Poulter, G. Panayi, M. Bofill and G. Goldstein,Rheumatoid arthritis: a disease of T-lymphocyte/macrophage immunoregulation. LancetII, 839–842 (1981).

    Google Scholar 

  2. J. D. Taurog, G. P. Sandberg and M. L. Mahowald,The cellular basis of adjuvant arthritis. II. Characterisation of the cells mediating passive transfer. Cell. Immunol.80, 198–204 (1983).

    PubMed  Google Scholar 

  3. M. F. van den Broek, W. B. an den Berg and L. B. van de Putte,Monoclonal anti-Ia antibodies suppress the flare up reaction of antigen induced arthritis in mice. Clin. exp. Immunol.66, 320–330 (1986).

    PubMed  Google Scholar 

  4. R. Holmdahl, L. Klareskog, K. Rubin, J. Bjork, G. Smedegard, R. Jonsson and M. Andersson,Role of T-lymphocytes in murine collagen induced arthritis. Agents and Actions19, 295–305 (1986).

    PubMed  Google Scholar 

  5. O. Kohashi, Y. Kohashi, S. Kotani and A. Osawa,A new model of experimental arthritis induced by an aqueous form of synthetic adjuvant in immunodeficient rats (SHR and nude rats). Ryumachi21 Suppl., 149–155 (1981).

    PubMed  Google Scholar 

  6. O. Kohashi, K. Aihara, A. Ozawa, S. Kotani and I. Azuma,New model of a synthetic adjuvant, N-acetyl muramyl-l-alanyl-d-isoglutamine-induced arthritis. Clinical and histologic studies in athymic nude and euthymic rats. Lab. Invest.47, 27–36 (1982).

    PubMed  Google Scholar 

  7. K. Takagishi, N. Kaibara, T. Hotokobuchi, C. Arita, M. Morinaga and K. Aral,Effects of cyclosporin on collagen induced arthritis in mice. Ann. Rheum. Dis.45, 339–344 (1986).

    PubMed  Google Scholar 

  8. D. E. Trentham, R. A. Dynesius and J. R. David,Passive transfer by cells of type II collagen-induced arthritis. J. Clin. Invest.62, 359–366 (1978).

    PubMed  Google Scholar 

  9. J. Holoshitz, Y. Naparstek, A. Ben-Nun and I. R. Cohen,Lines of T-lymphocytes induce or vaccinate against autoimmune arthritis. Science219, 56–58 (1983).

    PubMed  Google Scholar 

  10. R. Holmdahl, L. Klareskog, K. Rubin, E. Larsson and H. Wigzell,T-lymphocytes in collagen II-specific T-cell lines and clones. Characterisation of arthritogenic collagen II-specific T-cell lines and clones. Scand. J. Immunol.22, 295–306 (1985).

    PubMed  Google Scholar 

  11. G. E. Ranges, S. Sriram and S. M. Cooper,Prevention of type II collagen-induced arthritis by in vivo treatment with anti-L 3 T 4. J. exp. Med.162, 1105–1110 (1985).

    PubMed  Google Scholar 

  12. J. T. Hom, L. D. Butler, P. E. Riedl and A. M. Bendele,The progression of the inflammation in established collagen-induced arthritis can be altered by treatment with immunological or pharmacological agents which inhibit T-cell activities. Eur. J. Immunol.18, 881–888 (1988).

    PubMed  Google Scholar 

  13. P. H. Wooley, H. S. Luthra, W. P. Lafuse, A. Huse, J. M. Sturart and C. S. David,Type II collagen-induced arthritis in mice. III. Suppression of arthritis by using monoclonal and polyclonal anti-Ia antisera. J. Immunol.134, 2366–2374 (1985).

    PubMed  Google Scholar 

  14. S. Banerjee, B.-Y. Wei, K. Hillman, H. S. Luthra and C. S. David,Immunosuppression of collagen-induced arthritis in mice with an anti-IL-2 receptor antibody. J. Immunol.141, 1150–1154 (1988).

    PubMed  Google Scholar 

  15. P. Larsson, R. Holmdahl, L. Bencker and L. Klareskog,In vivo treatment with W3/13 (anti-pan T) but not OX8 (anti-suppressor/cytotoxic T) monoclonal antibodies impedes the development of adjuvant arthritis. Immunology56, 383–391 (1985).

    PubMed  Google Scholar 

  16. K. M. Ferguson, H. Osawa, T. Diamantstein, A. L. Oronsky and S. S. Kerwer,Treatment with anti-interleukin 2 receptor antibody protects rats from passive but not active arthritis. Int. J. ImmunotherapyIV, 29–33 (1988).

    Google Scholar 

  17. M. E. J. Billingham, S. Fairchild, E. Griffin, L. Drayer and C. Hicks,Monoclonal antibody therapy for arthritis. InThe therapeutic control of inflammatory diseases. (ed. I. Otterness). Elsevier, New York (in press 1989).

    Google Scholar 

  18. C. Herzog, C. Walker, W. Pichler, A. Aeschlimann, P. Wassmer, H. Stockinger, W. Knapp, P. Rieber and W. Muller,Monoclonal anti-CD4 in arthritis. Lancetii, 1461–1462 (1987).

    Google Scholar 

  19. B. Kirkham, I. Chikanza, C. Pitzalis, G. H. Kingsley, R. Grahame, T. Gibson and G. Panayi,response to monoclonal CD7 antibody in rheumatoid arthritis. Lanceti, 588 (1988).

    Google Scholar 

  20. V. Kyle, R. J. Coughlan, H. Tiche, H. Waldmann and B. L. Hazleman,Beneficial effect of monoclonal antibody to interleukin 2 receptor on activated T-cells in rheumatoid arthritis. Ann. Rheum. Dis.48, 428–429 (1989).

    PubMed  Google Scholar 

  21. J. Gauldie, C. Richards, D. Harnish, P. Lansdorp and H. Baumann,Interferon beta 2/B-cell stimulatory factor 2 shares identity with monocyte derived hepatocyte-stimulating factor and regulates the major acute phase protein response in liver cells. Proc. Soc. Natl. Acad. Sci. USA84, 7251–7155 (1987).

    Google Scholar 

  22. M. E. J. Billingham,Models of arthritis and the search for anti-arthritic drugs. Pharmac. Ther.21, 389–428 (1983).

    Google Scholar 

  23. S. Ayad, M. Z. Abedin, S. M. Grundy and J. B. Weiss,Isolation and characterisation of an unusual collagen from hyaline cartilage and intervertebral disc. Febs. Letters123, 195–199 (1981).

    PubMed  Google Scholar 

  24. W. N. Erber, A. J. Pinching and D. W. Mason,Immunocytochemical detection of T and B populations in routine blood smears. Lanceti, 1042–1046 (1984).

    Google Scholar 

  25. W. A. Jefferies, J. R. Green and A. F. Williams,Authentic T helper CD4 (W3/25) antigen on rat peritoneal macrophages. J. exp. Med.162, 117–127 (1985).

    PubMed  Google Scholar 

  26. V. H. Perry and S. Gordon,Modulation of CD4 antigen on macrophages and microglia in rat brain. J. exp. Med.166, 1138–1143 (1987).

    PubMed  Google Scholar 

  27. F. C. Breedveld, R. Dynesius-Trentham, M. de Sousa and D. E. Trentham,Collagen arthritis in the rat is initiated by CD4+T cells and can be amplified by iron. Cell. Immunol.121, 1–12 (1989).

    PubMed  Google Scholar 

  28. R. J. Benjamin and H. Waldmann,Induction of tolerance by monoclonal antibody therapy. Nature320, 449–451 (1986).

    PubMed  Google Scholar 

  29. R. J. Benjamin, S. X. Qin, W. P. Wise, S. P. Cobbold and H. Waldmann,Mechanisms of monoclonal antibody-facilitated tolerance induction: a possible role for the CD4 (L 3 T 4)and CD11a (LFA-1) molecules in self-non-self discrimination. Eur. J. Immunol.18, 1079–1088 (1988).

    PubMed  Google Scholar 

  30. L. Riechmann, M. Clark, H. Waldmann and G. Winter,Reshaping human antibodies for therapy. Nature332, 323–327 (1988).

    PubMed  Google Scholar 

  31. H. Acha-Orbea, D. J. Mitchell, L. Timmermann, D. C. Wraith, G. S. Tausch, M. K. Waldor, S. S. Zamvil, H. O. McDevitt and L. Steinman,Limited heterogeneity of T-cell receptors from lymphocytes mediating autoimmune encephalomyelitis allows specific immune intervention. Cell54, 263–273 (1988).

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Connective Tissue Disease Research, Lilly Research Centre Ltd., Eli Lilly & Co., Erl Wood Manor, Windlesham, Surrey, UK

    M. E. J. Billingham, C. Hicks & S. Carney

Authors
  1. M. E. J. Billingham
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. Hicks
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Carney
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Billingham, M.E.J., Hicks, C. & Carney, S. Monoclonal antibodies and arthritis. Agents and Actions 29, 77–87 (1990). https://doi.org/10.1007/BF01964727

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01964727

Keywords

Search

Navigation