Published in:
01-07-2009
Oral Tolerization with Cardiac Myosin Peptide (614–629) Ameliorates Experimental Autoimmune Myocarditis: Role of Stat 6 Genes in BALB/CJ Mice
Published in: Journal of Clinical Immunology | Issue 4/2009
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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.