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Contribution of the innate immune system to autoimmune myocarditis: a role for complement

Nature Immunology volume 2, pages 739–745 (2001)Cite this article

Abstract

Myocarditis is a principal cause of heart disease among young adults and is often a precursor of heart failure due to dilated cardiomyopathy. We show here that complement is critical for the induction of experimental autoimmune myocarditis and that it acts through complement receptor type 1 (CR1) and type 2 (CR2). We also found a subset of CD44hiCD62Llo T cells that expresses CR1 and CR2 and propose that both receptors are involved in the expression of B and T cell activation markers, T cell proliferation and cytokine production. These findings provide a mechanism by which activated complement, a key product of the innate immune response, modulates the induction of an autoimmune disease.

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Figure 1: Depletion of C3.
Figure 2: Blockade of CR1 and CR2.
Figure 3: Histological examination of the hearts of mice treated with mAb 7G6 or controls.
Figure 4: Immunization of CR+/+ and CR−/− mice with cardiac myosin.
Figure 5: Expression of CD69, B7-1 and B7-2.
Figure 6: Expression of CD44 and CD62L on the surface of T cells.
Figure 7: Expression of CR1 and CR2 on a subset of CD44hiCD62Llo T cells.

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Acknowledgements

We thank P. Caturegli, E. A. Stafford, M. V. Talor, W. M. Baldwin III, S. Mirshahidi and C. L. Burek for critically reading the manuscript and for technical advice. Supported by NIH grants ES07141, HL33878, HL65100 (to N. R. R.) and AI31105 (to V. M. H.). Z. K. was supported by the Deutsche Herzstiftung. T. T. was supported by the Deutsche Forschungsgemeinschaft.

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Authors and Affiliations

  1. Department of Pathology, The Johns Hopkins School of Medicine, Baltimore, 21205, MD, USA

    Ziya Kaya, Marina Afanasyeva, Yan Wang, K. Malte Dohmen, Jens Schlichting, DeLisa Fairweather & Noel R. Rose

  2. The W. Harry Feinstone, Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, 21205, MD, USA

    Marina Afanasyeva, DeLisa Fairweather & Noel R. Rose

  3. Department of Molecular Biology and Genetics, The Johns Hopkins School of Medicine, Baltimore, 21205, MD, USA

    Theresa Tretter

  4. Departments of Medicine and Immunology, University of Colorado Health Science Center, Denver, 80262, CO, USA

    V. Michael Holers

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Kaya, Z., Afanasyeva, M., Wang, Y. et al. Contribution of the innate immune system to autoimmune myocarditis: a role for complement. Nat Immunol 2, 739–745 (2001). https://doi.org/10.1038/90686

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