Oral tolerization with cardiac myosin peptide (614-629) ameliorates experimental autoimmune myocarditis: role of STAT 6 genes in BALB/CJ mice.

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-gamma production versus wild type, while STAT 4(-/-) mice had decreased proliferation and INF-gamma. 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.