Zhang Mingqiang, Shi Xiaohu, Zhao Jingquan, Guo Wenjia, Zhou Jie
Department of Respiratory and Critical Care Medicine, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, P.R. China.
Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, P.R. China.
Biomed Rep. 2023 Jul 17;19(2):55. doi: 10.3892/br.2023.1637. eCollection 2023 Aug.
The roles of myeloid-derived suppressor cells (MDSCs) and regulatory T-cells (Tregs) in acute myocardial infarction (AMI) remain elusive. The present study aimed to analyze the proportions of the granulocytic and monocytic populations of MDSCs (G-MDSCs and M-MDSCs, respectively), and Tregs in the peripheral blood mononuclear cells (PBMCs) of patients with AMI. The present study recruited 34 patients with AMI and 37 healthy controls without clinical signs of myocardial ischemia. PBMCs were isolated from the peripheral blood samples of patients with AMI within 24 h following admission to the hospital and from those of the healthy controls during a physical examination. Two subsets of MDSCs, G-MDSCs (CD15CD33CD11bCD14HLA-DR) and M-MDSCs (CD14CD15CD11bHLA-DR), and Tregs (CD3CD4CD25CD127 T-cells) in the PBMCs derived from the patients with AMI and healthy controls were analyzed using flow cytometry. The effects of MDSCs derived from patients with AMI on naïve CD4 T-cells were examined in the co-culture system. The results revealed that the proportions of G-MDSCs and M-MDSCs were higher in the peripheral blood of patients with AMI than in that of the healthy controls. The patients with AMI had significantly higher numbers of programmed death-ligand (PD-L)1- and PD-L2-positive G-MDSCs and M-MDSCs compared with the healthy controls (P<0.05). The MDSCs could acquire a granulocytic phenotype following AMI, and the G-MDSCs and M-MDSCs would be more likely to express PD-L2 and PD-L1, respectively. The ratios of Tregs to CD4 T-cells and PD-1 Tregs in the peripheral blood of patients with AMI were significantly higher than those in the healthy controls (P<0.05). The results of flow cytometry demonstrated an increase in the numbers of inducible Tregs in the co-culture system with the G-MDSCs derived from patients with AMI compared with the G-MDSCs derived from the healthy controls (P<0.01). On the whole, the findings presented herein demonstrate the accumulation of MDSCs, and the upregulation of PD-L1 and PD-L2 expression on the surface of MDSCs in patients with AMI. MDSCs can induce the expansion of Tregs by binding PD-1 on the surface of Tregs, thus playing a crucial role in AMI.
髓源性抑制细胞（MDSCs）和调节性T细胞（Tregs）在急性心肌梗死（AMI）中的作用仍不清楚。本研究旨在分析AMI患者外周血单个核细胞（PBMCs）中粒细胞样和单核细胞样MDSCs（分别为G-MDSCs和M-MDSCs）以及Tregs的比例。本研究招募了34例AMI患者和37例无心肌缺血临床症状的健康对照。在入院后24小时内从AMI患者外周血样本中分离PBMCs，并在体检时从健康对照者外周血样本中分离PBMCs。采用流式细胞术分析AMI患者和健康对照者PBMCs中MDSCs的两个亚群，即G-MDSCs（CD15⁺CD33⁺CD11b⁺CD14⁻HLA-DR⁻）和M-MDSCs（CD14⁻CD15⁺CD11b⁺HLA-DR⁻），以及Tregs（CD3⁺CD4⁺CD25⁺CD127⁻T细胞）。在共培养系统中检测AMI患者来源的MDSCs对初始CD4⁺T细胞的影响。结果显示，AMI患者外周血中G-MDSCs和M-MDSCs的比例高于健康对照者。与健康对照者相比，AMI患者PD-L1和PD-L2阳性的G-MDSCs和M-MDSCs数量显著增加（P<0.05）。AMI后MDSCs可获得粒细胞样表型，且G-MDSCs和M-MDSCs分别更易表达PD-L2和PD-L1。AMI患者外周血中Tregs与CD4⁺T细胞的比例以及PD-1⁺Tregs比例显著高于健康对照者（P<0.05）。流式细胞术结果显示，与健康对照者来源的G-MDSCs相比，在与AMI患者来源的G-MDSCs共培养系统中，诱导性Tregs数量增加（P<0.0）。总体而言，本文研究结果表明AMI患者中存在MDSCs的蓄积，且MDSCs表面PD-L1和PD-L2表达上调。MDSCs可通过结合Tregs表面的PD-1诱导Tregs扩增，从而在AMI中发挥关键作用。
