Abstract
DBA/2 and Balb/c mice, both H-2d, develop myocardial inflammation and necrosis when infected with a heart-adapted strain of coxsackievirus Group B, Type 3. Similar inoculation of C57Bl/6 (H-2b) animals results in minimal myocarditis despite equivalent heart virus titers in the three stains. Thus, the host's genetic constitution influences the pathogenesis of the infection. Anti-mouse thymocyte serum and monoclonal Iad antibody effectively prevent myocarditis induction in DBA/2 and Balb/c mice, which demonstrates the importance of the immune system in this disease. Cytolytic T lymphocytes lysing virus-infected and uninfected myocytes and heart-reactive autoantibodies occur in both myocarditis-susceptible strains. Cellular immunity causes the myocardial injury in Balb/c mice. Complement depletion of Balb/c mice using cobra venom factor fails to alter the disease. Similar treatment of DBA/2 animals abrogates inflammation and necrosis, which suggests that heart-reactive antibodies in this strain are primarily responsible for initiating myocardial damage.
Full text
PDF![284](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73a6/1888112/ec1efcf8e035/amjpathol00161-0098.png)
![285](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73a6/1888112/3a029bb33337/amjpathol00161-0099.png)
![286](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73a6/1888112/5732c3b72c6d/amjpathol00161-0100.png)
![287](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73a6/1888112/837ae487ea8b/amjpathol00161-0101.png)
![288](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73a6/1888112/0c9a868b5280/amjpathol00161-0102.png)
![289](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73a6/1888112/dcc4c60141b1/amjpathol00161-0103.png)
![290](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73a6/1888112/4bd521c9a43d/amjpathol00161-0104.png)
![291](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73a6/1888112/4ff9ee63e497/amjpathol00161-0105.png)
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Cobbold S. P., Waldmann H. A rapid solid-phase enzyme-linked binding assay for screening monoclonal antibodies to cell surface antigens. J Immunol Methods. 1981;44(2):125–133. doi: 10.1016/0022-1759(81)90340-9. [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]
- Guthrie M., Lodge P. A., Huber S. A. Cardiac injury in myocarditis induced by Coxsackievirus group B, type 3 in Balb/c mice is mediated by Lyt 2 + cytolytic lymphocytes. Cell Immunol. 1984 Oct 15;88(2):558–567. doi: 10.1016/0008-8749(84)90188-6. [DOI] [PubMed] [Google Scholar]
- Huber S. A., Job L. P. Cellular immune mechanisms in Coxsackievirus group B, type 3 induced myocarditis in Balb/C mice. Adv Exp Med Biol. 1983;161:491–508. doi: 10.1007/978-1-4684-4472-8_29. [DOI] [PubMed] [Google Scholar]
- Huber S. A., Job L. P. Differences in cytolytic T cell response of BALB/c mice infected with myocarditic and non-myocarditic strains of coxsackievirus group B, type 3. Infect Immun. 1983 Mar;39(3):1419–1427. doi: 10.1128/iai.39.3.1419-1427.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Huber S. A., Lodge P. A. Coxsackievirus B-3 myocarditis in Balb/c mice. Evidence for autoimmunity to myocyte antigens. Am J Pathol. 1984 Jul;116(1):21–29. [PMC free article] [PubMed] [Google Scholar]
- Huber S. A., Lyden D. C., Lodge P. A. Immunopathogenesis of experimental Coxsackievirus induced myocarditis: role of autoimmunity. Herz. 1985 Feb;10(1):1–7. [PubMed] [Google Scholar]
- Maisch B., Bülowius U., Schmier K., Klopf D., Koper D., Sibelis T., Kochsiek K. Immunological cellular regulator and effector mechanisms in myocarditis. Herz. 1985 Feb;10(1):8–14. [PubMed] [Google Scholar]
- Maisch B., Deeg P., Liebau G., Kochsiek K. Diagnostic relevance of humoral and cytotoxic immune reactions in primary and secondary dilated cardiomyopathy. Am J Cardiol. 1983 Nov 1;52(8):1072–1078. doi: 10.1016/0002-9149(83)90535-0. [DOI] [PubMed] [Google Scholar]
- Nilsson U. R., Müller-Eberhard H. J. Deficiency of the fifth component of complement in mice with an inherited complement defect. J Exp Med. 1967 Jan 1;125(1):1–16. doi: 10.1084/jem.125.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shapiro M. E., Burakoff S. J., Benacerraf B., Finberg R. W. Ir gene control of the cytotoxic T lymphocyte response to Sendai virus: H-2k mice are low responders to Sendai. J Immunol. 1981 Dec;127(6):2571–2574. [PubMed] [Google Scholar]
- Wolfgram L. J., Beisel K. W., Rose N. R. Heart-specific autoantibodies following murine coxsackievirus B3 myocarditis. J Exp Med. 1985 May 1;161(5):1112–1121. doi: 10.1084/jem.161.5.1112. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wong C. Y., Woodruff J. J., Woodruff J. F. Generation of cytotoxic T lymphocytes during coxsackievirus B-3 infection. I. Model and viral specificity1. J Immunol. 1977 Apr;118(4):1159–1164. [PubMed] [Google Scholar]
- Woodruff J. F. Viral myocarditis. A review. Am J Pathol. 1980 Nov;101(2):425–484. [PMC free article] [PubMed] [Google Scholar]
- Woodruff J. F., Woodruff J. J. Involvement of T lymphocytes in the pathogenesis of coxsackie virus B3 heart disease. J Immunol. 1974 Dec;113(6):1726–1734. [PubMed] [Google Scholar]