Myocardial infarction triggers cardioprotective antigen-specific T helper cell responses
Myocardial infarction triggers cardioprotective antigen-specific T helper cell responses
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DOI：
10.1172/jci123859
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发表时间：
2019-11-01
影响因子：
15.9
通讯作者：
Ramos, Gustavo Campos
中科院分区：
文献类型：
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作者：
Rieckmann, Max;Delgobo, Murilo;Ramos, Gustavo Campos
T细胞的自身反应性是自身免疫性疾病的一个标志，但也有助于自我维持和促进组织修复。在这里，我们调查了心脏特异性T细胞在心肌梗死(MI)方面是有益的还是有害的影响，心肌梗死是全球主要的死亡原因。在筛选了150多个II类限制性表位后，我们发现肌球蛋白重链α(MYHCA)是触发Balb/c小鼠心肌梗死后CD4(+)T细胞活化的主要心脏抗原。转移的MYHCA(614-629)特异性CD4(+)T细胞(TCR-M细胞)选择性地聚集在梗死小鼠的心肌和纵隔淋巴结(MED-LNS)中，获得具有明显促愈基因表达谱的Treg表型，并介导心脏保护。在心肌梗死患者的尸检样本中也检测到了心肌Tregs。使用CXCR4放射性配基的非侵入性PET/CT成像显示，MI患者的中层淋巴结增大，细胞密度增加。值得注意的是，在心肌梗塞患者中观察到的MED-LN改变与梗塞范围和心功能相关。综上所述，我们的研究结果提供了MI背景诱导小鼠持续T细胞自身免疫的证据，并证实了MI患者中存在类似的心脏/中层/T细胞轴。
T cell autoreactivity is a hallmark of autoimmune diseases but can also benefit self-maintenance and foster tissue repair. Here, we investigated whether heart-specific T cells exert salutary or detrimental effects in the context of myocardial infarction (MI), the leading cause of death worldwide. After screening more than 150 class II-restricted epitopes, we found that myosin heavy chain alpha (MYHCA) was a dominant cardiac antigen triggering post-MI CD4(+)T cell activation in Balb/c mice. Transferred MYHCA(614-629)-specific CD4(+)T cells (TCR-M cells) selectively accumulated in the myocardium and mediastinal lymph nodes (med-LNs) of infarcted mice, acquired a Treg phenotype with a distinct prohealing gene expression profile, and mediated cardioprotection. Myocardial Tregs were also detected in autopsy samples from patients who had had a MI. Noninvasive PET/CT imaging using a CXCR4 radioligand revealed enlarged med-LNs with increased cellularity in patients with MI. Notably, the med-LN alterations observed in MI patients correlated with the infarct size and cardiac function. Taken together, the results obtained in our study provide evidence that MI context induces prohealing T cell autoimmunity in mice and confirm the existence of an analogous heart/med-LN/T cell axis in patients with MI.