Skip to main content
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1994 Jun;96(3):470–475. doi: 10.1111/j.1365-2249.1994.tb06053.x

Anti-alpha beta T cell receptor antibody prevents the progression of experimental autoimmune myocarditis.

H Hanawa 1, M Kodama 1, T Inomata 1, T Izumi 1, A Shibata 1, M Tuchida 1, Y Matsumoto 1, T Abo 1
PMCID: PMC1534574  PMID: 8004817

Abstract

We investigated the effects of anti-alpha beta T cell receptor antibody in rat experimental autoimmune myocarditis (EAM), using a new animal model of autoimmune myocarditis characterized by the appearance of multinucleated giant cells. EAM was induced by injecting Lewis rats subcutaneously in the footpads with 1.0 mg of human cardiac myosin in an equal volume of Freund's complete adjuvant (FCA) on days 0 and 7. In experiment 1, we evaluated the effect of long-term anti-alpha beta TCR antibody therapy on prevention of progression of EAM. Long-term administration of anti-alpha beta TCR antibody prevented progression of EAM in a dose-dependent manner. Flow cytometry performed at the time of sacrifice showed that the percentage of alpha beta T cells in lymph nodes and spleen was similar in the control group and the group in which almost no histologic evidence of myocarditis was found. In experiment 2, we examined the effects of short-term therapy. Rats were killed at different stages and pathologic specimens were examined. Short-term therapy delayed the onset of myocarditis. Results of flow cytometry suggested that impairment of antigen recognition or T cell function by occupancy of the TCR rather than depletion of TCR was the mechanism responsible for suppression of EAM.

Full text

PDF
470

Images in this article

Selected References

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

  1. Bender J. R. Idiopathic dilated cardiomyopathy. An immunologic, genetic, or infectious disease, or all of the above? Circulation. 1991 Feb;83(2):704–706. doi: 10.1161/01.cir.83.2.704. [DOI] [PubMed] [Google Scholar]
  2. Daly K., Richardson P. J., Olsen E. G., Morgan-Capner P., McSorley C., Jackson G., Jewitt D. E. Acute myocarditis. Role of histological and virological examination in the diagnosis and assessment of immunosuppressive treatment. Br Heart J. 1984 Jan;51(1):30–35. doi: 10.1136/hrt.51.1.30. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Davies M. J., Ward D. E. How can myocarditis be diagnosed and should it be treated? Br Heart J. 1992 Oct;68(4):346–347. doi: 10.1136/hrt.68.10.346. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Estrin M., Smith C., Huber S. Coxsackievirus B-3 myocarditis. T-cell autoimmunity to heart antigens is resistant to cyclosporin-A treatment. Am J Pathol. 1986 Nov;125(2):244–251. [PMC free article] [PubMed] [Google Scholar]
  5. Gilbert E. M., O'Connell J. B., Hammond M. E., Renlund D. G., Watson F. S., Bristow M. R. Treatment of myocarditis with OKT3 monoclonal antibody. Lancet. 1988 Apr 2;1(8588):759–759. doi: 10.1016/s0140-6736(88)91555-3. [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. Hanawa H., Kodama M., Zhang S., Izumi T., Shibata A. An immunosuppressant compound, FK-506, prevents the progression of autoimmune myocarditis in rats. Clin Immunol Immunopathol. 1992 Mar;62(3):321–326. doi: 10.1016/0090-1229(92)90110-a. [DOI] [PubMed] [Google Scholar]
  8. Hanawa H., Tsuchida M., Matsumoto Y., Watanabe H., Abo T., Sekikawa H., Kodama M., Zhang S., Izumi T., Shibata A. Characterization of T cells infiltrating the heart in rats with experimental autoimmune myocarditis. Their similarity to extrathymic T cells in mice and the site of proliferation. J Immunol. 1993 Jun 15;150(12):5682–5695. [PubMed] [Google Scholar]
  9. Hohlfeld R., Engel A. G., Ii K., Harper M. C. Polymyositis mediated by T lymphocytes that express the gamma/delta receptor. N Engl J Med. 1991 Mar 28;324(13):877–881. doi: 10.1056/NEJM199103283241303. [DOI] [PubMed] [Google Scholar]
  10. Holoshitz J., Koning F., Coligan J. E., De Bruyn J., Strober S. Isolation of CD4- CD8- mycobacteria-reactive T lymphocyte clones from rheumatoid arthritis synovial fluid. Nature. 1989 May 18;339(6221):226–229. doi: 10.1038/339226a0. [DOI] [PubMed] [Google Scholar]
  11. Huber S. A., Moraska A., Choate M. T cells expressing the gamma delta T-cell receptor potentiate coxsackievirus B3-induced myocarditis. J Virol. 1992 Nov;66(11):6541–6546. doi: 10.1128/jvi.66.11.6541-6546.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hünig T., Wallny H. J., Hartley J. K., Lawetzky A., Tiefenthaler G. A monoclonal antibody to a constant determinant of the rat T cell antigen receptor that induces T cell activation. Differential reactivity with subsets of immature and mature T lymphocytes. J Exp Med. 1989 Jan 1;169(1):73–86. doi: 10.1084/jem.169.1.73. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jung S., Krämer S., Schluesener H. J., Hünig T., Toyka K., Hartung H. P. Prevention and therapy of experimental autoimmune neuritis by an antibody against T cell receptors-alpha/beta. J Immunol. 1992 Jun 15;148(12):3768–3775. [PubMed] [Google Scholar]
  14. Kishimoto C., Abelmann W. H. Monoclonal antibody therapy for prevention of acute coxsackievirus B3 myocarditis in mice. Circulation. 1989 Jun;79(6):1300–1308. doi: 10.1161/01.cir.79.6.1300. [DOI] [PubMed] [Google Scholar]
  15. Kodama M., Matsumoto Y., Fujiwara M. In vivo lymphocyte-mediated myocardial injuries demonstrated by adoptive transfer of experimental autoimmune myocarditis. Circulation. 1992 May;85(5):1918–1926. doi: 10.1161/01.cir.85.5.1918. [DOI] [PubMed] [Google Scholar]
  16. Kodama M., Matsumoto Y., Fujiwara M., Masani F., Izumi T., Shibata A. A novel experimental model of giant cell myocarditis induced in rats by immunization with cardiac myosin fraction. Clin Immunol Immunopathol. 1990 Nov;57(2):250–262. doi: 10.1016/0090-1229(90)90039-s. [DOI] [PubMed] [Google Scholar]
  17. Lanier L. L., Weiss A. Presence of Ti (WT31) negative T lymphocytes in normal blood and thymus. Nature. 1986 Nov 20;324(6094):268–270. doi: 10.1038/324268a0. [DOI] [PubMed] [Google Scholar]
  18. Mason J. W., Billingham M. E., Ricci D. R. Treatment of acute inflammatory myocarditis assisted by endomyocardial biopsy. Am J Cardiol. 1980 May;45(5):1037–1044. doi: 10.1016/0002-9149(80)90174-5. [DOI] [PubMed] [Google Scholar]
  19. Muir P., Nicholson F., Tilzey A. J., Signy M., English T. A., Banatvala J. E. Chronic relapsing pericarditis and dilated cardiomyopathy: serological evidence of persistent enterovirus infection. Lancet. 1989 Apr 15;1(8642):804–807. doi: 10.1016/s0140-6736(89)92270-8. [DOI] [PubMed] [Google Scholar]
  20. Murakami U., Uchida K., Hiratsuka T. Cardiac myosin from pig heart ventricle. Purification and enzymatic properties. J Biochem. 1976 Sep;80(3):611–619. doi: 10.1093/oxfordjournals.jbchem.a131316. [DOI] [PubMed] [Google Scholar]
  21. O'Connell J. B. Immunosuppression for dilated cardiomyopathy. N Engl J Med. 1989 Oct 19;321(16):1119–1121. doi: 10.1056/NEJM198910193211609. [DOI] [PubMed] [Google Scholar]
  22. Sempé P., Bédossa P., Richard M. F., Villà M. C., Bach J. F., Boitard C. Anti-alpha/beta T cell receptor monoclonal antibody provides an efficient therapy for autoimmune diabetes in nonobese diabetic (NOD) mice. Eur J Immunol. 1991 May;21(5):1163–1169. doi: 10.1002/eji.1830210511. [DOI] [PubMed] [Google Scholar]
  23. Sigal N. H., Dumont F. J. Cyclosporin A, FK-506, and rapamycin: pharmacologic probes of lymphocyte signal transduction. Annu Rev Immunol. 1992;10:519–560. doi: 10.1146/annurev.iy.10.040192.002511. [DOI] [PubMed] [Google Scholar]
  24. Smith S. C., Allen P. M. Myosin-induced acute myocarditis is a T cell-mediated disease. J Immunol. 1991 Oct 1;147(7):2141–2147. [PubMed] [Google Scholar]
  25. Yoshino S., Cleland L. G. Depletion of alpha/beta T cells by a monoclonal antibody against the alpha/beta T cell receptor suppresses established adjuvant arthritis, but not established collagen-induced arthritis in rats. J Exp Med. 1992 Apr 1;175(4):907–915. doi: 10.1084/jem.175.4.907. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Yoshino S., Cleland L. G., Mayrhofer G., Brown R. R., Schwab J. H. Prevention of chronic erosive streptococcal cell wall-induced arthritis in rats by treatment with a monoclonal antibody against the T cell antigen receptor alpha beta. J Immunol. 1991 Jun 15;146(12):4187–4189. [PubMed] [Google Scholar]
  27. Yoshino S., Schlipköter E., Kinne R., Hünig T., Emmrich F. Suppression and prevention of adjuvant arthritis in rats by a monoclonal antibody to the alpha/beta T cell receptor. Eur J Immunol. 1990 Dec;20(12):2805–2808. doi: 10.1002/eji.1830201241. [DOI] [PubMed] [Google Scholar]
  28. Zhang S., Kodama M., Hanawa H., Izumi T., Shibata A., Masani F. Effects of cyclosporine, prednisolone and aspirin on rat autoimmune giant cell myocarditis. J Am Coll Cardiol. 1993 Apr;21(5):1254–1260. doi: 10.1016/0735-1097(93)90254-x. [DOI] [PubMed] [Google Scholar]

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

RESOURCES