Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
Eur Heart J. 2019 Dec 21;40(48):3924-3933. doi: 10.1093/eurheartj/ehz516.
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.
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-γ, granzyme B, and perforin.
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.
心肌梗死后持续的心脏 T 细胞反应与随后的不良心室重构和心力衰竭进展有关。关于缺血性衰竭人类心脏中 T 细胞受体（TCR） repertoire 变化与表型特征相结合的 T 细胞，尚无数据。
使用高通量测序分析 TCR repertoire 发现，与对照心脏中的 T 细胞相比，缺血性衰竭心脏中的 T 细胞表现出克隆性扩张的 TCR repertoire，但 TRBV-J 重排和 V 基因片段的使用模式相似；与外周血中的 T 细胞相比，缺血性衰竭心脏中的 T 细胞表现出受限和克隆性扩张的 TCR repertoire，以及 TRBV-J 重排和 V 基因片段的不同使用模式，提示缺血性衰竭心脏中发生了组织特异性 T 细胞扩张。一致地，缺血性衰竭心脏中 TCR 克隆型共享明显，尤其是在 HLA 等位基因共享的患者心脏中。此外，缺血性心力衰竭（IHF）患者外周血中的 IHF 心脏相关克隆型比对照组更频繁。心脏浸润 T 细胞显示出记忆和效应样特征。CD4+T 细胞中以 Th1 细胞为主；CD8+T 细胞与 CD4+T 细胞数量相当，并产生高水平的干扰素-γ、颗粒酶 B 和穿孔素。
我们提供了新的证据，表明缺血性衰竭人类心脏中存在以 Th1 细胞和细胞毒性 CD8+T 细胞为主的组织特异性 T 细胞反应，这可能有助于心力衰竭的进展。
