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

被引：16

作者：

Gonnella, Patricia A. ^{[1
,2
,3
]}

Del Nido, Pedro J. ^{[2
,3
]}

McGowan, Francis X. ^{[2
,3
]}

机构：

[1] Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Boston, MA 02115 USA

[3] Childrens Hosp, Boston, MA 02115 USA

来源：

JOURNAL OF CLINICAL IMMUNOLOGY | 2009年 / 29卷 / 04期

关键词：

Myocarditis; inflammation; autoimmunity; cytokines; MYELIN BASIC-PROTEIN; LYMPHOID-TISSUE GALT; CD4(+) T-CELLS; INFLAMMATORY CYTOKINES; DILATED CARDIOMYOPATHY; EXPRESSION; INDUCTION; TOLERANCE; IL-12; RESPONSES;

D O I：

10.1007/s10875-009-9290-z

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Experimental autoimmune myocarditis (EAM) is mediated by myocardial infiltration by myosin-specific T cells secreting inflammatory cytokines. 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). 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. These results demonstrate that oral tolerization ameliorates EAM in BALB/CJ mice and indicate a down-regulatory role for STAT 6 genes.

引用

页码：434 / 443

页数：10