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急性冠状动脉综合征患者中,共抑制分子程序性死亡配体1(PD-L1)在CD4⁺CD25⁺FOXP3⁺调节性T细胞上的表达升高。

Expression of coinhibitory PD-L1 on CD4⁺CD25⁺FOXP3⁺ regulatory T cells is elevated in patients with acute coronary syndrome.

作者信息

Li Si-Hui, Chen Wei-Jun, Yan Min, Shu Yan-Wen, Liao Yu-Hua

机构信息

Department of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.

出版信息

Coron Artery Dis. 2015 Nov;26(7):598-603. doi: 10.1097/MCA.0000000000000282.

Abstract

OBJECTIVE

Coronary heart disease (CHD) is associated with high morbidity and mortality worldwide. CD4⁺CD25⁺FOXP3⁺ regulatory T cells (Tregs) play a role in the modulation of vascular inflammation. The negatively costimulatory molecule programmed cell death ligand 1 (PD-L1) exerts a prominent effect on the adjustment of immune responses. We investigated the relationship between the expression of PD-L1 on peripheral blood Tregs and the severity of CHD.

METHODS AND RESULTS

Human peripheral blood was collected from 59 patients with CHD and 11 healthy volunteers. The expression of PD-L1 on peripheral blood Tregs was detected by flow cytometry, and the production of interleukin 2 (IL-2), IL-4, IL-10, and transforming growth factor β1 in plasma was determined using enzyme-linked immunosorbent assay. The subgroup of patients with acute coronary syndrome (ACS), which includes unstable angina pectoris, non-ST-segment elevation myocardial infarction, and ST-segment elevation myocardial infarction, showed a significant reduction of FOXP3 and PD-L1 expression on Tregs compared with the subgroup of patients with chronic coronary artery disease, comprising stable angina pectoris, silent myocardial ischemia, and ischemic heart failure, and the control group. Moreover, the ACS group showed significantly increased production of IL-2, and decreased production of IL-4, IL-10, and transforming growth factor β1, compared with the coronary artery disease and control groups.

CONCLUSION

Expression of the coinhibitory molecule PD-L1 on peripheral blood Tregs is correlated negatively with the severity of CHD and could serve as a novel indicator of ACS.

摘要

目的

冠心病(CHD)在全球范围内具有高发病率和死亡率。CD4⁺CD25⁺FOXP3⁺调节性T细胞(Tregs)在调节血管炎症中发挥作用。负性共刺激分子程序性细胞死亡配体1(PD-L1)对免疫反应的调节具有显著影响。我们研究了外周血Tregs上PD-L1的表达与CHD严重程度之间的关系。

方法与结果

从59例冠心病患者和11名健康志愿者中采集人外周血。采用流式细胞术检测外周血Tregs上PD-L1的表达,并用酶联免疫吸附测定法测定血浆中白细胞介素2(IL-2)、IL-4、IL-10和转化生长因子β1的产生。急性冠状动脉综合征(ACS)亚组包括不稳定型心绞痛、非ST段抬高型心肌梗死和ST段抬高型心肌梗死,与慢性冠状动脉疾病亚组(包括稳定型心绞痛、无症状心肌缺血和缺血性心力衰竭)及对照组相比,其Tregs上FOXP3和PD-L1的表达显著降低。此外,与冠状动脉疾病组和对照组相比,ACS组IL-2的产生显著增加,而IL-4、IL-10和转化生长因子β1的产生减少。

结论

外周血Tregs上共抑制分子PD-L1的表达与CHD严重程度呈负相关,可作为ACS的一种新指标。

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