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.
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.
Authors: D Bryant; L Becker; J Richardson; J Shelton; F Franco; R Peshock; M Thompson; B Giroir Journal: Circulation Date: 1998-04-14 Impact factor: 29.690
Authors: M Afanasyeva; Y Wang; Z Kaya; E A Stafford; K M Dohmen; A A Sadighi Akha; N R Rose Journal: Circulation Date: 2001-12-18 Impact factor: 29.690
Authors: K Takeda; T Tanaka; W Shi; M Matsumoto; M Minami; S Kashiwamura; K Nakanishi; N Yoshida; T Kishimoto; S Akira Journal: Nature Date: 1996-04-18 Impact factor: 49.962