Skip to main content
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1994 Dec;98(3):442–447. doi: 10.1111/j.1365-2249.1994.tb05510.x

Anti-CD5 therapy decreases severity of established disease in collagen type II-induced arthritis in DBA/1 mice.

C Plater-Zyberk 1, P C Taylor 1, M G Blaylock 1, R N Maini 1
PMCID: PMC1534513  PMID: 7527741

Abstract

Collagen-induced arthritis has been widely used as an animal model of rheumatoid arthritis. We have used this model with a view to determining potential therapeutic targets for the treatment of human disease. To do this we have attempted to modulate the progression of established arthritis over a 10-day time period following the first appearance of disease, by i.p. injection of one of three different MoAbs. These consist of a rat IgG2a specific for the CD5 antigen expressed on all T cells and a subpopulation of B cells, a mouse IgG2b recognizing the CD72 antigen, and a rat IgM specific for the B220 molecule, CD72 and B220 both being expressed on all B cells. None of the three MoAbs had depleting activity in vivo. The progression of arthritis was monitored both clinically, and histologically. The effects of treatment with anti-CD5 and anti-CD72 antibodies were compared with control antibodies of the same species class and subclass. In the case of anti-B220 antibodies, the effects of treatment were compared with administration of PBS. Of these MoAbs, only treatment with anti-CD5 resulted in disease amelioration with significant decrease in disease severity in 60% of the animals. These changes became apparent 6 days after initiation of treatment. There were no significant differences in serum levels of IgG antibodies to native bovine collagen type II between the groups of treated and control mice. Possible mechanisms underlying the modification of disease expression following treatment with anti-CD5 MoAb are discussed.

Full text

PDF
442

Images in this article

Selected References

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

  1. Benjamin R. J., Waldmann H. Induction of tolerance by monoclonal antibody therapy. Nature. 1986 Apr 3;320(6061):449–451. doi: 10.1038/320449a0. [DOI] [PubMed] [Google Scholar]
  2. Casali P., Burastero S. E., Nakamura M., Inghirami G., Notkins A. L. Human lymphocytes making rheumatoid factor and antibody to ssDNA belong to Leu-1+ B-cell subset. Science. 1987 Apr 3;236(4797):77–81. doi: 10.1126/science.3105056. [DOI] [PubMed] [Google Scholar]
  3. Ceuppens J. L., Baroja M. L. Monoclonal antibodies to the CD5 antigen can provide the necessary second signal for activation of isolated resting T cells by solid-phase-bound OKT3. J Immunol. 1986 Sep 15;137(6):1816–1821. [PubMed] [Google Scholar]
  4. Courtenay J. S., Dallman M. J., Dayan A. D., Martin A., Mosedale B. Immunisation against heterologous type II collagen induces arthritis in mice. Nature. 1980 Feb 14;283(5748):666–668. doi: 10.1038/283666a0. [DOI] [PubMed] [Google Scholar]
  5. Elliott M. J., Maini R. N., Feldmann M., Long-Fox A., Charles P., Katsikis P., Brennan F. M., Walker J., Bijl H., Ghrayeb J. Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to tumor necrosis factor alpha. Arthritis Rheum. 1993 Dec;36(12):1681–1690. doi: 10.1002/art.1780361206. [DOI] [PubMed] [Google Scholar]
  6. Goldschmidt T. J., Holmdahl R. Anti-T cell receptor antibody treatment of rats with established autologous collagen-induced arthritis: suppression of arthritis without reduction of anti-type II collagen autoantibody levels. Eur J Immunol. 1991 May;21(5):1327–1330. doi: 10.1002/eji.1830210536. [DOI] [PubMed] [Google Scholar]
  7. Goldschmidt T. J., Holmdahl R. Therapeutic effects of monoclonal antibodies to alpha beta TCR but not to CD4 on collagen-induced arthritis in the rat. Cell Immunol. 1994 Mar;154(1):240–248. doi: 10.1006/cimm.1994.1072. [DOI] [PubMed] [Google Scholar]
  8. Hardy R. R., Hayakawa K., Shimizu M., Yamasaki K., Kishimoto T. Rheumatoid factor secretion from human Leu-1+ B cells. Science. 1987 Apr 3;236(4797):81–83. doi: 10.1126/science.3105057. [DOI] [PubMed] [Google Scholar]
  9. Hom J. T., Butler L. D., Riedl P. E., Bendele A. M. The progression of the inflammation in established collagen-induced arthritis can be altered by treatments with immunological or pharmacological agents which inhibit T cell activities. Eur J Immunol. 1988 Jun;18(6):881–888. doi: 10.1002/eji.1830180608. [DOI] [PubMed] [Google Scholar]
  10. Horneff G., Burmester G. R., Emmrich F., Kalden J. R. Treatment of rheumatoid arthritis with an anti-CD4 monoclonal antibody. Arthritis Rheum. 1991 Feb;34(2):129–140. doi: 10.1002/art.1780340202. [DOI] [PubMed] [Google Scholar]
  11. Hutchings P., O'Reilly L., Parish N. M., Waldmann H., Cooke A. The use of a non-depleting anti-CD4 monoclonal antibody to re-establish tolerance to beta cells in NOD mice. Eur J Immunol. 1992 Jul;22(7):1913–1918. doi: 10.1002/eji.1830220735. [DOI] [PubMed] [Google Scholar]
  12. Kirkham B. W., Pitzalis C., Kingsley G. H., Chikanza I. C., Sabharwal S., Barbatis C., Grahame R., Gibson T., Amlot P. L., Panayi G. S. Monoclonal antibody treatment in rheumatoid arthritis: the clinical and immunological effects of a CD7 monoclonal antibody. Br J Rheumatol. 1991 Dec;30(6):459–463. doi: 10.1093/rheumatology/30.6.459. [DOI] [PubMed] [Google Scholar]
  13. Ledbetter J. A., June C. H., Grosmaire L. S., Rabinovitch P. S. Crosslinking of surface antigens causes mobilization of intracellular ionized calcium in T lymphocytes. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1384–1388. doi: 10.1073/pnas.84.5.1384. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Maeda T., Saikawa I., Hotokebuchi T., Sugioka Y., Eto M., Murakami Y., Nomoto K. Exacerbation of established collagen-induced arthritis in mice treated with an anti-T cell receptor antibody. Arthritis Rheum. 1994 Mar;37(3):406–413. doi: 10.1002/art.1780370315. [DOI] [PubMed] [Google Scholar]
  15. Martin P. J., Hansen J. A., Siadak A. W., Nowinski R. C. Monoclonal antibodies recognizing normal human T lymphocytes and malignant human B lymphocytes: a comparative study. J Immunol. 1981 Nov;127(5):1920–1923. [PubMed] [Google Scholar]
  16. Osman N., Lazarovits A. I., Crumpton M. J. Physical association of CD5 and the T cell receptor/CD3 antigen complex on the surface of human T lymphocytes. Eur J Immunol. 1993 May;23(5):1173–1176. doi: 10.1002/eji.1830230530. [DOI] [PubMed] [Google Scholar]
  17. Osman N., Ley S. C., Crumpton M. J. Evidence for an association between the T cell receptor/CD3 antigen complex and the CD5 antigen in human T lymphocytes. Eur J Immunol. 1992 Nov;22(11):2995–3000. doi: 10.1002/eji.1830221135. [DOI] [PubMed] [Google Scholar]
  18. Plater-Zyberk C., Maini R. N., Lam K., Kennedy T. D., Janossy G. A rheumatoid arthritis B cell subset expresses a phenotype similar to that in chronic lymphocytic leukemia. Arthritis Rheum. 1985 Sep;28(9):971–976. doi: 10.1002/art.1780280903. [DOI] [PubMed] [Google Scholar]
  19. Strand V., Lipsky P. E., Cannon G. W., Calabrese L. H., Wiesenhutter C., Cohen S. B., Olsen N. J., Lee M. L., Lorenz T. J., Nelson B. Effects of administration of an anti-CD5 plus immunoconjugate in rheumatoid arthritis. Results of two phase II studies. The CD5 Plus Rheumatoid Arthritis Investigators Group. Arthritis Rheum. 1993 May;36(5):620–630. doi: 10.1002/art.1780360508. [DOI] [PubMed] [Google Scholar]
  20. Stuart J. M., Townes A. S., Kang A. H. Collagen autoimmune arthritis. Annu Rev Immunol. 1984;2:199–218. doi: 10.1146/annurev.iy.02.040184.001215. [DOI] [PubMed] [Google Scholar]
  21. Stuart J. M., Townes A. S., Kang A. H. Nature and specificity of the immune response to collagen in type II collagen-induced arthritis in mice. J Clin Invest. 1982 Mar;69(3):673–683. doi: 10.1172/JCI110495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sun D., Branum K., Sun Q. Prevention of experimental autoimmune encephalomyelitis in Lewis rats by treatment with an anti-rat CD5 antibody (OX19). Cell Immunol. 1992 Dec;145(2):263–271. doi: 10.1016/0008-8749(92)90330-r. [DOI] [PubMed] [Google Scholar]
  23. Van de Velde H., von Hoegen I., Luo W., Parnes J. R., Thielemans K. The B-cell surface protein CD72/Lyb-2 is the ligand for CD5. Nature. 1991 Jun 20;351(6328):662–665. doi: 10.1038/351662a0. [DOI] [PubMed] [Google Scholar]
  24. Verwilghen J., Kingsley G. H., Ceuppens J. L., Panayi G. S. Inhibition of synovial fluid T cell proliferation by anti-CD5 monoclonal antibodies. A potential mechanism for their immunotherapeutic action in vivo. Arthritis Rheum. 1992 Dec;35(12):1445–1451. doi: 10.1002/art.1780351207. [DOI] [PubMed] [Google Scholar]
  25. Williams R. O., Feldmann M., Maini R. N. Anti-tumor necrosis factor ameliorates joint disease in murine collagen-induced arthritis. Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9784–9788. doi: 10.1073/pnas.89.20.9784. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Williams R. O., Williams D. G., Feldmann M., Maini R. N. Increased limb involvement in murine collagen-induced arthritis following treatment with anti-interferon-gamma. Clin Exp Immunol. 1993 May;92(2):323–327. doi: 10.1111/j.1365-2249.1993.tb03399.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Wooley P. H., Luthra H. S., Stuart J. M., David C. S. Type II collagen-induced arthritis in mice. I. Major histocompatibility complex (I region) linkage and antibody correlates. J Exp Med. 1981 Sep 1;154(3):688–700. doi: 10.1084/jem.154.3.688. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Yoshino S., Cleland L. G., Mayrhofer G. Treatment of collagen-induced arthritis in rats with a monoclonal antibody against the alpha/beta T cell antigen receptor. Arthritis Rheum. 1991 Aug;34(8):1039–1047. doi: 10.1002/art.1780340814. [DOI] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES