Pathologic T-cell response in ischaemic failing hearts elucidated by T-cell receptor sequencing and phenotypic characterization
Pathologic T-cell response in ischaemic failing hearts elucidated by T-cell receptor sequencing and phenotypic characterization
复制标题
通过 T 细胞受体测序和表型表征阐明缺血性衰竭心脏的病理性 T 细胞反应。
DOI：
10.1093/eurheartj/ehz516
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发表时间：
2019-12-21
影响因子：
39.3
通讯作者：
Cheng, Xiang
中科院分区：
文献类型：
--
作者：
Tang, Ting-Ting;Zhu, Yi-Cheng;Cheng, Xiang
心肌梗死引发的持续性心脏T细胞反应与随后的心室重塑和心力衰竭进展有关。方法与结果用高通量测序技术分析缺血性心力衰竭患者T细胞TCR谱，发现缺血性心力衰竭患者T细胞TCR谱克隆性扩增，但TRBV-J重排和V基因片段的使用模式与对照组相似;与外周血T细胞相比，缺血性心力衰竭患者的T细胞表现出有限的和克隆性扩增的TCR库以及TRBV-J重排和V基因片段的不同使用模式，表明缺血性心力衰竭患者发生组织特异性T细胞扩增。一致的是，TCR克隆型共享在缺血性衰竭心脏中是突出的，特别是在共享人类白细胞抗原（HLA）等位基因的患者的心脏中。此外，缺血性心力衰竭（IHF）心脏相关的克隆型更常见于外周血中的IHF患者比对照组。心脏浸润性T细胞显示记忆和效应样特征。Th 1细胞在CD 4（+）T细胞中占优势; CD 8（+）T细胞与CD 4（+）T细胞一样丰富，并产生高水平的干扰素-c、颗粒酶B，结论我们为Th 1细胞和细胞毒性CD 8（+）占主导地位的组织特异性T细胞应答提供了新的证据。缺血性心力衰竭患者心脏中的T细胞可能导致心力衰竭的进展。
Aims A persistent cardiac T-cell response initiated by myocardial infarction is linked to subsequent adverse ventricular remodelling and progression of heart failure. No data exist on T-cell receptor (TCR) repertoire changes in combination with phenotypic characterization of T cells in ischaemic failing human hearts.Methods and results Analysis of TCR repertoire with high-throughput sequencing revealed that compared with T cells in control hearts, those in ischaemic failing hearts showed a clonally expanded TCR repertoire but similar usage patterns of TRBV-J rearrangements and V gene segments; compared with T cells in peripheral blood, those in ischaemic failing hearts exhibited a restricted and clonally expanded TCR repertoire and different usage patterns of TRBV-J rearrangements and V gene segments, suggesting the occurrence of tissue-specific T-cell expansion in ischaemic failing hearts. Consistently, TCR clonotype sharing was prominent in ischaemic failing hearts, especially in hearts of patients who shared human leucocyte antigen (HLA) alleles. Furthermore, ischaemia heart failure (IHF) heart-associated clonotypes were more frequent in peripheral blood of IHF patients than in that of controls. Heart-infiltrating T cells displayed memory- and effector-like characteristics. Th1 cells were the predominant phenotype among CD4(+) T cells; CD8(+) T cells were equally as abundant as CD4(+) T cells and produced high levels of interferon-c, granzyme B, and perforin.Conclusion We provide novel evidence for a tissue-specific T-cell response predominated by Th1 cells and cytotoxic CD8(+) T cells in ischaemic failing human hearts that may contribute to the progression of heart failure.