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Oral Tolerization with Cardiac Myosin Peptide (614–629) Ameliorates Experimental Autoimmune Myocarditis: Role of Stat 6 Genes in BALB/CJ Mice

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Abstract

Introduction

Experimental autoimmune myocarditis (EAM) is mediated by myocardial infiltration by myosin-specific T cells secreting inflammatory cytokines.

Materials and methods

To clarify the role of cytokines in EAM, we compared STAT 6-deficient (−/−) with STAT 4−/− and wild-type (BALB/CJ) mice following immunization with cardiac myosin peptide (614–629).

Results

Wild-type mice developed severe disease with a small increase in severity in STAT 6−/− mice, while STAT 4−/− mice were resistant to EAM. STAT 6−/− mice had increased splenocyte proliferation and INF-γ production versus wild type, while STAT 4−/− mice had decreased proliferation and INF-γ. Following oral administration of myosin (614–629), tolerization was induced in wild-type mice evidenced by amelioration of myocarditis and up-regulation of IL-4. Adoptive transfer of splenocytes from orally tolerized mice resulted in inhibition of disease in STAT 6−/− mice.

Conclusion

These results demonstrate that oral tolerization ameliorates EAM in BALB/CJ mice and indicate a down-regulatory role for STAT 6 genes.

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Acknowledgments

This work was supported by grant # HL052589 from the NIH.

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Authors and Affiliations

  1. Children’s Hospital and Harvard Medical School, 320 Longwood Ave., Boston, MA, 02115, USA

    Patricia A. Gonnella, Pedro J. Del Nido & Francis X. McGowan

  2. Beth Israel Deaconess Medical Center and Harvard Medical School, Dana Research Bldg. #863, 330 Brookline Ave., Boston, MA, 02115, USA

    Patricia A. Gonnella

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  1. Patricia A. Gonnella
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Correspondence to Patricia A. Gonnella.

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Gonnella, P.A., Del Nido, P.J. & McGowan, F.X. Oral Tolerization with Cardiac Myosin Peptide (614–629) Ameliorates Experimental Autoimmune Myocarditis: Role of Stat 6 Genes in BALB/CJ Mice. J Clin Immunol 29, 434–443 (2009). https://doi.org/10.1007/s10875-009-9290-z

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