Recombinant cardiac myosin fragment induces experimental autoimmune myocarditis via activation of Th1 and Th17 immunity.
Recombinant cardiac myosin fragment induces experimental autoimmune myocarditis via activation of Th1 and Th17 immunity.
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DOI：
10.1080/08916930802167902
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发表时间：
2008-09
期刊：
影响因子：
3.5
通讯作者：
Engman DM
中科院分区：
文献类型：
--
作者：
Daniels MD;Hyland KV;Wang K;Engman DM
辅助性T细胞（Th）免疫应答在A/J小鼠实验性自身免疫性心肌炎（EAM）诱导、进展和消退中的特异性和功能尚不清楚。已发表的数据表明，参与的Th 1和Th 2的反应，EAM，然而，以前无法评估抗原特异性在体内和体外T细胞反应的心肌肌球蛋白免疫的动物混淆了我们的理解，这一重要模型的自身免疫性心肌炎。我们研究的目的是开发一种基于心肌肌球蛋白重组片段的EAM替代模型，希望重组蛋白将允许测量功能性T细胞反应，这是纯化的天然蛋白质所不可能的。用跨越氨基酸1074-1646的心脏肌球蛋白的重组片段（称为Myo 4）免疫的A/J小鼠在免疫后三周发生严重的心肌炎，其特征在于心脏肥大、大量单核细胞浸润和纤维化。小鼠还产生了特异于Myo 4和纯化的心肌肌球蛋白的IgG 1显性体液免疫应答。用Myo 4体外刺激从Myo 4免疫的动物收获的脾细胞导致细胞增殖，并分别优先产生Th 1和Th 17相关细胞因子IFN-γ、IL-17和IL-6。相比之下，IL-4的产生可以忽略不计。本研究描述了一种新的EAM模型，诱导免疫与心肌肌球蛋白的特定片段，从抗原特异性分析揭示了Th 1和Th 17免疫的重要性。
The specificity and function of T helper (Th) immune responses underlying the induction, progression, and resolution of experimental autoimmune myocarditis (EAM) in A/J mice are unclear. Published data suggest involvement of both Th1 and Th2 responses in EAM; however, the previous inability to assess antigen-specific in vivo and in vitro T cell responses in cardiac myosin immunized animals has confounded our understanding of this important model of autoimmune myocarditis. The goal of our study was to develop an alternative model of EAM based on a recombinant fragment of cardiac myosin, in hopes that the recombinant protein will permit measurement of functional T cell responses that is not possible with purified native protein. A/J mice immunized with a recombinant fragment of cardiac myosin spanning amino acids 1074–1646, termed Myo4, developed severe myocarditis characterized by cardiac hypertrophy, massive mononuclear cell infiltration and fibrosis, three weeks post-immunization. The mice also developed an IgG1 dominant humoral immune response specific for both Myo4 and purified cardiac myosin. The in vitro stimulation of splenocytes harvested from Myo4-immunized animals with Myo4 resulted in cellular proliferation with preferential production of the Th1- and Th17-associated cytokines, IFN-γ, IL-17 and IL-6, respectively. Production of IL-4 was negligible by comparison. This study describes a new model of EAM, inducible by immunization with a specific fragment of cardiac myosin, from which antigen-specific analyses reveal an importance for both Th1 and Th17 immunity.
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