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. 1984 Jul;116(1):21–29.

Coxsackievirus B-3 myocarditis in Balb/c mice. Evidence for autoimmunity to myocyte antigens.

S A Huber, P A Lodge
PMCID: PMC1900366  PMID: 6331168

Abstract

Male Balb/c mice inoculated with a heart-adapted variant of Coxsackievirus, group B, type 3 (Nancy) (CVB3M), develop extensive myocarditis and cytolytic activity to primary cultures of uninfected and infected myocytes. To elucidate the mechanisms of myocyte injury in myocarditis, two distinct cytolytic T-lymphocyte (CTL) populations were isolated by immunoadsorption of lymph node cells to glutaraldehyde-fixed uninfected and infected myocyte monolayers. One population preferentially adsorbed to and lysed uninfected myocytes (autoreactive CTLs), while the other adsorbed to and lysed CVB3M-infected myocytes (virus-specific CTL). Neither CTL population adsorbed to monolayers of HeLa, L929, or umbilical cord endothelial cells, or to myocytes infected with a related but nonmyocarditic Coxsackievirus B-3 variant ( CVB3o ). While both autoreactive and virus-specific CTLs induced myocarditis in vivo, the lesions caused by autoreactive CTLs were more extensive and necrotizing than those of virus-specific cells. These results support the hypothesis that CVB3 -induced myocarditis results, in part, from autoimmunity to myocyte antigens.

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Selected References

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

  1. Adler K. B., Brody A. R., Craighead J. E. Studies on the mechanism of mucin secretion by cells of the porcine tracheal epithelium. Proc Soc Exp Biol Med. 1981 Jan;166(1):96–106. doi: 10.3181/00379727-166-41030. [DOI] [PubMed] [Google Scholar]
  2. BENIRSCHKE K., KIBRICK S. Acute aseptic myocarditis and meningoencephalitis in the newborn child infected with coxsackle virus group B, type 3. N Engl J Med. 1956 Nov 8;255(19):883–889. doi: 10.1056/NEJM195611082551902. [DOI] [PubMed] [Google Scholar]
  3. FLETCHER E., BRENNAN C. F. Cardiac complications of Coxsackie-virus infection. Lancet. 1957 May 4;272(6975):913–915. doi: 10.1016/s0140-6736(57)91229-1. [DOI] [PubMed] [Google Scholar]
  4. Feinstone S. M., Hensley G. T., Rytel M. W. Post-coxsackie virus B3 myocardiopathy in mice. Proc Soc Exp Biol Med. 1973 Oct 1;144(1):345–350. [PubMed] [Google Scholar]
  5. 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]
  6. GODMAN G. C., BUNTING H., MELNICK J. L. The histopathology of Coxsackie virus infection in mice. I. Morphologic observations with four different viral types. Am J Pathol. 1952 Mar-Apr;28(2):223–257. [PMC free article] [PubMed] [Google Scholar]
  7. GRODUMS E. I., DEMPSTER G. Myocarditis in experimental Coxsackie B-3 infection. Can J Microbiol. 1959 Dec;5:605–615. doi: 10.1139/m59-074. [DOI] [PubMed] [Google Scholar]
  8. Gauntt C. J., Trousdale M. D., LaBadie D. R., Paque R. E., Nealon T. Properties of coxsackievirus B3 variants which are amyocarditic or myocarditic for mice. J Med Virol. 1979;3(3):207–220. doi: 10.1002/jmv.1890030307. [DOI] [PubMed] [Google Scholar]
  9. Hirschman S. Z., Hammer G. S. Coxsackie virus myopericarditis. A microbiological and clinical review. Am J Cardiol. 1974 Aug;34(2):224–232. doi: 10.1016/0002-9149(74)90201-x. [DOI] [PubMed] [Google Scholar]
  10. Huber S. A., Job L. P., Auld K. R., Woodruff J. F. Sex-related differences in the rapid production of cytotoxic spleen cells active against uninfected myofibers during Coxsackievirus B-3 infection. J Immunol. 1981 Apr;126(4):1336–1340. [PubMed] [Google Scholar]
  11. 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]
  12. 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]
  13. Huber S. A., Job L. P., Woodruff J. F. Lysis of infected myofibers by coxsackievirus B-3-immune T lymphocytes. Am J Pathol. 1980 Mar;98(3):681–694. [PMC free article] [PubMed] [Google Scholar]
  14. JAVETT S. N., HEYMANN S., MUNDEL B., PEPLER W. J., LURIE H. I., GEAR J., MEASROCH V., KIRSCH Z. Myocarditis in the new newborn infant; a study of an outbreak associated with Coxsackie group B virus infection in a maternity home in Johannesburg. J Pediatr. 1956 Jan;48(1):1–22. doi: 10.1016/s0022-3476(56)80111-x. [DOI] [PubMed] [Google Scholar]
  15. Jaffe E. A., Nachman R. L., Becker C. G., Minick C. R. Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Invest. 1973 Nov;52(11):2745–2756. doi: 10.1172/JCI107470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lerner A. M., Wilson F. M. Virus myocardiopathy. Prog Med Virol. 1973;15:63–91. [PubMed] [Google Scholar]
  17. 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]
  18. Sainani G. S., Krompotic E., Slodki S. J. Adult heart disease due to the Coxsackie virus B infection. Medicine (Baltimore) 1968 Mar;47(2):133–147. doi: 10.1097/00005792-196803000-00003. [DOI] [PubMed] [Google Scholar]
  19. Smith W. G. Coxsackie B myopericarditis in adults. Am Heart J. 1970 Jul;80(1):34–46. doi: 10.1016/0002-8703(70)90035-9. [DOI] [PubMed] [Google Scholar]
  20. Welsh R. M., Jr Mouse natural killer cells: induction specificity, and function. J Immunol. 1978 Nov;121(5):1631–1635. [PubMed] [Google Scholar]
  21. Wilson F. M., Miranda Q. R., Chason J. L., Lerner A. M. Residual pathologic changes following murine coxsackie A and B myocarditis. Am J Pathol. 1969 May;55(2):253–265. [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. Woodruff J. F., Kilbourne E. D. The influence of quantitated post-weaning undernutrition on coxsackievirus B3 infection of adult mice. I. Viral persistence and increased severity of lesions. J Infect Dis. 1970 Feb;121(2):137–163. doi: 10.1093/infdis/121.2.137. [DOI] [PubMed] [Google Scholar]
  24. Woodruff J. F. Viral myocarditis. A review. Am J Pathol. 1980 Nov;101(2):425–484. [PMC free article] [PubMed] [Google Scholar]
  25. 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]

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