Summary
This chapter describes four murine models of autoimmune diseases: two related to autoimmune myocarditis and two related to autoimmune thyroiditis. The first model, Coxsackie virus B3 (CB3)-induced myocarditis, results in the development of acute myocarditis in susceptible as well as resistant mouse strains, whereas chronic myocarditis develops only in genetically susceptible mice. CB3-induced myocarditis closely resembles the course of human myocarditis, which is believed to be initiated by viral infection. Mouse cardiac myosin heavy chain has been identified as the major antigen associated with the late chronic phase of viral myocarditis. The second model is cardiac myosin-induced experimental autoimmune myocarditis (EAM) and, in a modification, cardiac α-myosin heavy chain peptide-induced myocarditis. In the EAM model, cardiac myosin or the relevant peptide in Freund’s complete adjuvant (FCA)is injected subcutaneously into mice. The immune response, the histological changes, and the genetic susceptibility seen in EAM are similar to those of CB3-induced myocarditis. The third model is experimental autoimmune thyroiditis (EAT). EAT can be induced in genetically susceptible strains of mice by immunization with mouse thyroglobulin in FCA or lipopolysaccharide. Mice susceptible to EAT have the H-2Ak, H-2As, or H-2Aq alleles. We describe here a standard technique for the induction of EAT; it was developed in our laboratory and is widely used as a model for studying Hashimoto’s thyroiditis. The fourth model presented in this chapter is that of spontaneous autoimmune thyroiditis in NOD.H2h4 mice. These mice express the H-2Ak allele on an NOD genetic background and develop spontaneous thyroiditis, which is exacerbated with dietary iodine.
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References
Rose, N. R. and Hill, S. L. (1996) Autoimmune myocarditis. Int. J. Cardiol. 54, 171–175.
Rose, N. R. and Afanasyeva, M. (2003) From infection to autoimmunity: the adjuvant effect. ASM News 69, 32–137.
Rose, N. R., Neumann, D. A., and Herkowitz, A. (1992) Coxsackievirus myocarditis, in Advances in Internal Medicine (Stollerman, G. H, LaMont, J. T., Leonard, J. J., and Siperstein, M. D., eds.), Mosby-Year Book, St. Louis, MO, pp. 411–429.
Rose, N. R., Wolfgram, L. J., Herkowitz, A., and Beisel, K. W. (1986) Postinfectious autoimmunity: two distinct phases of Coxsackievirus B3-induced myocarditis. Ann. NY Acad. Sci. 475, 146–156.
Fairweather, D., Kaya, Z., Shellam, G. R., Lawson, C. M., and Rose, N. R. (2001) From infection to autoimmunity. J. Autoimmun. 16, 175–186.
Neu, N., Beisel, K. W., Traystman, M. D., Rose, N. R., and Craig, S. W. (1987) Autoantibodies specific for the cardiac myosin isoform are found in mice susceptible to Coxsackievirus B3-induced myocarditis. J. Immunol. 138, 2488–2492.
Neu, N., Rose, N. R., Beisel, K. W., Herskowitz, A., Gurri-Glass, G., and Craig, S. W. (1987) Cardiac myosin induces myocarditis in genetically predisposed mice. J. Immunol. 139, 3630–3636.
Eriksson, U., Kurrer, M. O., Sonderegger, I., Iezzi, G., Tafuri, A, Hunziker, L., et al. (2003) Activation of dendritic cells through the interleukin 1 receptor 1 is critical for the induction of autoimmune myocarditis. J. Exp. Med. 197, 323–331.
Pummerer, C. L., Luze, K., Grassl, G., Bachmaier, K., Offner, F., Burrell, S. K., et al. (1996) Identification of cardiac myosin peptides capable of inducing autoimmune myocarditis in BALB/c mice. J. Clin. Invest. 97, 2057–2062.
Donermeyer, D. L., Beisel, K. W., Allen, P. M., and Smith, S. C. (1995) Myocarditis-inducing epitope of myosin binds constitutively and stably to I-Ak on antigen-presenting cells in the heart. J. Exp. Med. 182, 1291–1300.
Vladutiu, A. O. and Rose, N. R. (1975) Cellular basis of the genetic control of immune responsiveness to murine thyroglobulin in mice. Cell. Immunol. 17, 106–113.
Rasooly, L., Burek, C. L., and Rose, N. R. (1996) Iodine-induced autoimmune thyroiditis in NOD-H-2h4 mice. Clin. Immunol. Immunopathol. 81, 287–292.
Braley-Mullen, H., Sharp, G. C., Medling, B., and Tang, H. (1999) Spontaneous autoimmune thyroiditis in NOD.H-2h4 mice. J. Autoimmun. 12, 157–165.
Shiverick, K. T., Thomas, L. L., and Alpert, N. R. (1975) Purification of cardiac myosin. Application to hypertrophied myocardium. Biochim. Biophys. Acta 393, 124–133.
Tomazic, V. and Rose, N. R. (1977) Autoimmune murine thyroiditis IX. Relationship of humoral and cellular immunity to thyroiditis in high and low responder mice. Eur. J. Immunol. 7, 40–43.
El Rehewy, M., Kong, Y. M., Giraldo, A. A., and Rose, N. R. (1981) Syngeneic thyroglobulin is immunogenic in good responder mice. Eur. J. Immunol. 11, 146–151.
Rose, N. R., Twarog, F. J., and Crowle, A. J. (1971) Murine thyroiditis: importance of adjuvant and mouse strain for the induction of thyroid lesions. J. Immunol. 106, 698–704.
Zhang, W., Flynn, J. C., and Kong, Y. C. (2001) IL-12 prevents tolerance induction with mouse thyroglobulin by priming pathogenic T cells in experimental autoimmune thyroiditis: role of IFN-gamma and the costimulatory molecules CD40l and CD28. Cell. Immunol. 208, 52–61.
Braley-Mullen, H., Johnson, M., Sharp, G. C., and Kyriakos, M. (1985) Induction of experimental autoimmune thyroiditis in mice with in vitro activated splenic T cells. Cell. Immunol. 93, 132–143.
Parish, N. M., Roitt, I. M., and Cooke, A. (1988) Phenotypic characteristics of cells involved in induced suppression to murine experimental autoimmune thyroiditis. Eur. J. Immunol. 18, 1463–1467.
Esquivel, P. S., Rose, N. R., and Kong, Y. C. (1977) Induction of autoimmunity in good and poor responder mice with mouse thyroglobulin and lipopolysaccharide. J. Exp. Med. 145, 1250–1263.
Zaccone, P., Fehervari, Z., and Cooke, A. (2003) Tumour necrosis factor-alpha is a fundamental cytokine in autoimmune thyroid disease induced by thyroglobulin and lipopolysaccharide in interleukin-12 p40 deficient C57BL/6 mice. Immunology 108, 50–54.
Rose, N. R., Kong, Y. C., Okayasu, I., Giraldo, A. A., Beisel, K., and Sundick, R. S. (1981) T-cell regulation in autoimmune thyroiditis. Immunol Rev. 55, 299–314.
Balasa, B. and Carayanniotis, G. (1993) Immunotargeting of thyroglobulin on antigen presenting cells abrogates natural tolerance in the absence of adjuvant. Cell. Immunol. 150, 453–458.
Rasooly, L., Burek, C. L., and Rose, N. R. (1996) Iodine-induced autoimmune thyroiditis in NOD-H2h4 mice. Clin. Immunol. Immunopathol. 81, 287–292.
Kong, Y. M., Waldmann, H., Cobbold, S., Giraldo, A. A., Fuller, B. E., and Simon, L. L.(1989) Pathogenic mechanisms in murine autoimmune thyroiditis: short-and long-term effects of in vivo depletion of CD4+ and CD8+ cells. Clin. Exp. Immunol. 77, 428–433.
Twarog, F. J. and Rose, N. R. (1969) The adjuvant effect of pertussis vaccine in experimental thyroiditis of the rat. Proc. Soc. Exp. Biol. Med. 130, 434–439.
Lillehoj, H. S. and Rose, N. R. (1982) Humoral and cellular immune response to thyroglobulin in different inbred rat strains. Clin. Exp. Immunol. 47, 661–669.
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© 2004 Humana Press Inc., Totowa, NJ
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Čiháková, D., Sharma, R.B., Fairweather, D., Afanasyeva, M., Rose, N.R. (2004). Animal Models for Autoimmune Myocarditis and Autoimmune Thyroiditis. In: Perl, A. (eds) Autoimmunity. Methods in Molecular Medicine™, vol 102. Humana Press. https://doi.org/10.1385/1-59259-805-6:175
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DOI: https://doi.org/10.1385/1-59259-805-6:175
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