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Cited by 175Viral Infections and Immunology ResearchCardiac Fibrosis and RemodelingT-cell and B-cell Immunology

Experimental Autoimmune Myocarditis in A/J mice Is an Interleukin-4-Dependent Disease with a Th2 Phenotype

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Afanasyeva, Marina, Wang, Yan, Kaya, Ziya, Park, Sung, Zilliox, Michael J., Schofield, Brian H., Hill, Susan L., Rose, Noel R.·2001·The American Journal of Pathology
DOI 10.1016/s0002-9440(10)61685-9PMC PMC1850414
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Abstract

Myocarditis in humans is often associated with an autoimmune process in which cardiac myosin (CM) is a major autoantigen. Experimental autoimmune myocarditis (EAM) is induced in mice by immunization with CM. We found that EAM in A/J mice exhibits a Th2-like phenotype demonstrated by the histological picture of the heart lesions (eosinophils and giant cells) and by the humoral response (association of IgG1 response with disease and up-regulation of total IgE). Blocking interleukin (IL)-4 with anti-IL-4 monoclonal antibody (mAb) reduced the severity of EAM. This reduction in severity was associated with a shift from a Th2-like to a Th1-like phenotype represented by a reduction in CM-specific IgG1; an increase in CM-specific IgG2a; an abrogation of total IgE response; a decrease in IL-4, IL-5, and IL-13; as well as a dramatic increase in interferon (IFN)-gamma production in vitro. Based on the latter finding, we hypothesized that IFN-gamma limits disease. Indeed, IFN-gamma blockade with a mAb exacerbated disease. The ameliorating effect of IL-4 blockade was abrogated by co-administration of anti-IFN-gamma mAb. Thus, EAM represents a model of an organ-specific autoimmune disease associated with a Th2 phenotype, in which IL-4 promotes the disease and IFN-gamma limits it. Suppression of IFN-gamma represents at least one of the mechanisms by which IL-4 promotes EAM.

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  • A/J, BALB/c, and DBA/2 mice immunized with cardiac myosin show giant cell formation in the heart.

    “giant cell formation was also observed in the hearts of A/J, BALB/c, and DBA/2 mice when immunized with cardiac myosin”

    From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [59]

    The Cellular Composition of the Heart Infiltrate section and Figure 1 caption report giant cells in the hearts of A/J mice immunized with cardiac myosin. The paper describes eosinophil-rich heart lesions in BALB/c mice after cardiac-myosin immunization, but does not clearly report giant cells in that strain; the passages found do not address DBA/2 mice. (LLM, conf=0.88)

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Cited by

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Authors
Afanasyeva, M., Wang, Y., Kaya, Z., Park, S., Zilliox, M. J., Schofield, B. H., Hill, S. L., & Rose, N. R.
Affiliations
  • Johns Hopkins University (US)
  • Johns Hopkins Medicine (US)
Corresponding author
Rose, Noel R.
ORCID
Venue
The American Journal of Pathology
Publisher
Elsevier BV
Published
2001-07
Volume
159
Issue
1
Pages
193-203
ISSN
0002-9440 (ISSN-L)
DOI
10.1016/s0002-9440(10)61685-9
PMC
PMC1850414
OpenAlex
W2160440202
Cited by
175
References
2
Citations by year
2026: 1 · 2025: 4 · 2024: 8 · 2023: 7 · 2022: 6 · 2021: 4 · 2020: 5 · 2019: 2 · 2018: 2 · 2017: 7 · 2016: 6 · 2015: 7 · 2014: 7 · 2013: 6 · 2012: 9
FWCI
9.31
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • American Journal Of Pathology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Deutsche Herzstiftung
  • National Institutes of Health (1r21hl065100-01, ES03819, ES07141)
  • National Heart, Lung, and Blood Institute (HL-33878, R01HL033878, HL65100)
  • National Cancer Institute
  • National Institute of Environmental Health Sciences (ES 07141, ES03819, P30ES003819, T32ES007141)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Viral Infections and Immunology Research
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords
experimental autoimmune myocarditis, IL-4, Th2 phenotype, Th1/Th2 shift, interferon-gamma, A/J mice, IgE, IgG1, eosinophils, anti-IL-4 monoclonal antibody, anti-IFN-gamma monoclonal antibody, organ-specific autoimmunity, cytokine inhibition
MeSH terms
Animals, Antibodies, Monoclonal, Autoantibodies, Autoimmune Diseases, Cells, Cultured, Immunoglobulin E, Immunoglobulin G, Interferon-gamma, Mice, Inbred Strains, Myocarditis, Myocardium, Myosins, Phenotype, Severity of Illness Index, Spleen, Interleukin-4, Cytokines, Th2 Cells, Mice

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