Abstract
The pathogenesis of giant cell myocarditis remains unclear. Subsets of inflammatory infiltrating cells may reflect the pathogenesis and etiology of the disease. Therefore, we examined subsets of infiltrating mononuclear cells in the heart of the rat with experimental giant cell myocarditis. Lewis rats were immunized with cardiac myosin in Freund's complete adjuvant (FCA). Severe myocarditis characterized by congestive heart failure and multinucleated giant cells were elicited. The lesions were composed of predominant mononuclear cells, polymorphonuclear neutrophils and fragments of degenerated myocardial fibres. The subsets of infiltrating mononuclear cells were investigated using MoAbs against rat CD4+ T cell (W3/25), CD8+ T cell (CX8), B cell (OX33) and macrophage (OX42). By serial examination, bound immunoglobulin could only be found on degenerated myocardial fibres. In this model, most infiltrating mononuclear cells were composed of macrophages and CD4+ T cells. The frequencies of macrophages and CD4+ T cells were 73.7% and 13.8%, respectively. CD8+ T cells were scarce and B cells were rare in the lesions. The frequencies of CD8+ T cells and B cells were 4.5% and 0.4%, respectively. The dominance of macrophages and CD4+ T cells was the constant finding among the sites of the lesions and throughout the course of the disease. These characteristic subsets of infiltrating cells were in contrast to those of murine viral myocarditis which were mainly composed of natural killer (NK) cells and CD8+ T cells. Clarifying the subsets of infiltrating cells in myocarditis may contribute to differential diagnosis of myocarditis between viral and autoimmune types. From this study, the pathogenesis of experimental autoimmune giant cell myocarditis seemed to be closely related to CD4+ T cells and macrophages.
Full text
PDF





Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Cassling R. S., Linder J., Sears T. D., Waller B. F., Rogler W. C., Wilson J. E., Kugler J. D., Kay D. H., Dillon J. C., Slack J. D. Quantitative evaluation of inflammation in biopsy specimens from idiopathically failing or irritable hearts: experience in 80 pediatric and adult patients. Am Heart J. 1985 Oct;110(4):713–720. doi: 10.1016/0002-8703(85)90447-8. [DOI] [PubMed] [Google Scholar]
- DILLING N. V. Giant-cell myocarditis. J Pathol Bacteriol. 1956 Apr;71(2):295–300. doi: 10.1002/path.1700710204. [DOI] [PubMed] [Google Scholar]
- 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]
- Davidoff R., Palacios I., Southern J., Fallon J. T., Newell J., Dec G. W. Giant cell versus lymphocytic myocarditis. A comparison of their clinical features and long-term outcomes. Circulation. 1991 Mar;83(3):953–961. doi: 10.1161/01.cir.83.3.953. [DOI] [PubMed] [Google Scholar]
- Davies M. J., Pomerance A., Teare R. D. Idiopathic giant cell myocarditis--a distinctive clinico-pathological entity. Br Heart J. 1975 Feb;37(2):192–195. doi: 10.1136/hrt.37.2.192. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dec G. W., Jr, Palacios I. F., Fallon J. T., Aretz H. T., Mills J., Lee D. C., Johnson R. A. Active myocarditis in the spectrum of acute dilated cardiomyopathies. Clinical features, histologic correlates, and clinical outcome. N Engl J Med. 1985 Apr 4;312(14):885–890. doi: 10.1056/NEJM198504043121404. [DOI] [PubMed] [Google Scholar]
- Deguchi H., Hayashi T., Kotaka M., Nakayama Y., Kitaura Y., Kawamura K. In situ analysis with monoclonal antibodies of lymphocyte subsets in myocardial biopsies from patients with dilated cardiomyopathy and idiopathic (viral) myocarditis. Jpn Circ J. 1987 Dec;51(12):1365–1372. doi: 10.1253/jcj.51.1365. [DOI] [PubMed] [Google Scholar]
- Deguchi H., Kitaura Y., Hayashi T., Kotaka M., Kawamura K. Cell-mediated immune cardiocyte injury in viral myocarditis of mice and patients. Jpn Circ J. 1989 Jan;53(1):61–77. doi: 10.1253/jcj.53.61. [DOI] [PubMed] [Google Scholar]
- Fenoglio J. J., Jr, Ursell P. C., Kellogg C. F., Drusin R. E., Weiss M. B. Diagnosis and classification of myocarditis by endomyocardial biopsy. N Engl J Med. 1983 Jan 6;308(1):12–18. doi: 10.1056/NEJM198301063080103. [DOI] [PubMed] [Google Scholar]
- Godeny E. K., Gauntt C. J. In situ immune autoradiographic identification of cells in heart tissues of mice with coxsackievirus B3-induced myocarditis. Am J Pathol. 1987 Nov;129(2):267–276. [PMC free article] [PubMed] [Google Scholar]
- 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]
- Hosenpud J. D., McAnulty J. H., Niles N. R. Lack of objective improvement in ventricular systolic function in patients with myocarditis treated with azathioprine and prednisone. J Am Coll Cardiol. 1985 Oct;6(4):797–801. doi: 10.1016/s0735-1097(85)80485-x. [DOI] [PubMed] [Google Scholar]
- Humbert P., Faivre R., Fellman D., Bassand J. P., Dupond J. L. Giant cell myocarditis: an autoimmune disease? Am Heart J. 1988 Feb;115(2):485–487. doi: 10.1016/0002-8703(88)90505-4. [DOI] [PubMed] [Google Scholar]
- Kishimoto C., Abelmann W. H. Absence of effects of cyclosporine on myocardial lymphocyte subsets in Coxsackievirus B3 myocarditis in the aviremic stage. Circ Res. 1989 Oct;65(4):934–945. doi: 10.1161/01.res.65.4.934. [DOI] [PubMed] [Google Scholar]
- Kishimoto C., Kuribayashi K., Fukuma K., Masuda T., Tomioka N., Abelmann W. H., Kawai C. Immunologic identification of lymphocyte subsets in experimental murine myocarditis with encephalomyocarditis virus. Different kinetics of lymphocyte subsets between the heart and the peripheral blood, and significance of Thy 1.2+ (pan T) and Lyt 1+, 23+ (immature T) subsets in the development of myocarditis. Circ Res. 1987 Nov;61(5):715–725. doi: 10.1161/01.res.61.5.715. [DOI] [PubMed] [Google Scholar]
- Kishimoto C., Misaki T., Crumpacker C. S., Abelmann W. H. Serial immunologic identification of lymphocyte subsets in murine coxsackievirus B3 myocarditis: different kinetics and significance of lymphocyte subsets in the heart and in peripheral blood. Circulation. 1988 Mar;77(3):645–653. doi: 10.1161/01.cir.77.3.645. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Kodama M., Matsumoto Y., Fujiwara M., Zhang S. S., Hanawa H., Itoh E., Tsuda T., Izumi T., Shibata A. Characteristics of giant cells and factors related to the formation of giant cells in myocarditis. Circ Res. 1991 Oct;69(4):1042–1050. doi: 10.1161/01.res.69.4.1042. [DOI] [PubMed] [Google Scholar]
- Latham R. D., Mulrow J. P., Virmani R., Robinowitz M., Moody J. M. Recently diagnosed idiopathic dilated cardiomyopathy: incidence of myocarditis and efficacy of prednisone therapy. Am Heart J. 1989 Apr;117(4):876–882. doi: 10.1016/0002-8703(89)90626-1. [DOI] [PubMed] [Google Scholar]
- 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]
- Monrad E. S., Matsumori A., Murphy J. C., Fox J. G., Crumpacker C. S., Abelmann W. H. Therapy with cyclosporine in experimental murine myocarditis with encephalomyocarditis virus. Circulation. 1986 May;73(5):1058–1064. doi: 10.1161/01.cir.73.5.1058. [DOI] [PubMed] [Google Scholar]
- O'Connell J. B., Robinson J. A., Henkin R. E., Gunnar R. M. Immunosuppressive therapy in patients with congestive cardiomyopathy and myocardial uptake of gallium-67. Circulation. 1981 Oct;64(4):780–786. doi: 10.1161/01.cir.64.4.780. [DOI] [PubMed] [Google Scholar]
- Pyun K. S., Kim Y. H., Katzenstein R. E., Kikkawa Y. Giant cell myocarditis. Light and electron microscopic study. Arch Pathol. 1970 Aug;90(2):181–188. [PubMed] [Google Scholar]
- Saito T., Shiokawa A., Inoue S. Lymphatic subpopulations and their transition in myocardial tissue and peripheral blood of patients with biopsy-proven myocarditis. Jpn Circ J. 1989 Jan;53(1):1–6. doi: 10.1253/jcj.53.1. [DOI] [PubMed] [Google Scholar]
- Tanaka M., Ichinohasama R., Kawahara Y., Esaki Y., Hirokawa K., Okishige K., Tanaka Y. Acute idiopathic interstitial myocarditis: case report with special reference to morphological characteristics of giant cells. J Clin Pathol. 1986 Nov;39(11):1209–1216. doi: 10.1136/jcp.39.11.1209. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tomioka N., Kishimoto C., Matsumori A., Kawai C. Effects of prednisolone on acute viral myocarditis in mice. J Am Coll Cardiol. 1986 Apr;7(4):868–872. doi: 10.1016/s0735-1097(86)80349-7. [DOI] [PubMed] [Google Scholar]
- Zee-Cheng C. S., Tsai C. C., Palmer D. C., Codd J. E., Pennington D. G., Williams G. A. High incidence of myocarditis by endomyocardial biopsy in patients with idiopathic congestive cardiomyopathy. J Am Coll Cardiol. 1984 Jan;3(1):63–70. doi: 10.1016/s0735-1097(84)80431-3. [DOI] [PubMed] [Google Scholar]


