Impaired Thymic Export and Increased Apoptosis Account for Regulatory T Cell Defects in Patients with Non-ST Segment Elevation Acute Coronary Syndrome
Impaired Thymic Export and Increased Apoptosis Account for Regulatory T Cell Defects in Patients with Non-ST Segment Elevation Acute Coronary Syndrome
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胸腺输出受损和细胞凋亡增加是非 ST 段抬高急性冠状动脉综合征患者调节性 T 细胞缺陷的原因
DOI：
10.1074/jbc.m112.382978
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发表时间：
2012-10-05
影响因子：
4.8
通讯作者：
Cheng, Xiang
中科院分区：
文献类型：
--
作者：
Zhang, Wen-cai;Wang, Jun;Cheng, Xiang
调节性T（Treg）细胞对动脉粥样硬化的发展具有保护作用。先前的研究已经揭示了非ST段抬高急性冠状动脉综合征（NSTACS）患者的Treg细胞缺陷，但这些缺陷的机制仍不清楚。本研究发现NSTACS患者外周血CD 4（+）CD 25（+）CD 127（low）Treg细胞和CD 4（+）CD 25（+）CD 127（low）CD 45 RA（+）CD 45 RO（-）naive Treg细胞数量低于慢性稳定型心绞痛（CSA）和胸痛综合征（CPS）患者。然而，在所有组中，CD 4（+）CD 25（+）CD 127（低）CD 45 RA（-）CD 45 RO（+）记忆Treg细胞的数量相当。NSTACS患者胸腺内CD 4（+）、CD 25（+）、CD 127（低）、CD 45 RO（-）、CD 45 RA（+）、CD 31（+）新近移出的Treg细胞频率及纯化Treg细胞的T细胞受体切除环含量均低于CSA患者和CPS对照组。与CSA和CPS组相比，NSTACS组Treg细胞（定义为CD 4（+）CD 25（+）CD 127（low）annexinV（+）7-AAD（-））的自发性凋亡增加。氧化型LDL可诱导Treg细胞凋亡，NSTACS患者的氧化型LDL水平显著高于CSA和CPS组。根据Treg细胞水平的改变，NSTACS患者中TNF-α的浓度增加，导致IL-10/TNF-α比率降低。这些发现表明，受损的胸腺输出的Treg细胞和它们的增强的易感性，在外周细胞凋亡的NSTACS患者中观察到的Treg细胞缺陷负责。
Regulatory T (Treg) cells play a protective role against the development of atherosclerosis. Previous studies have revealed Treg cell defects in patients with non-ST elevation acute coronary syndrome (NSTACS), but the mechanisms underlying these defects remain unclear. In this study, we found that the numbers of peripheral blood CD4(+)CD25(+)CD127(low) Treg cells and CD4(+)CD25(+)CD127(low)CD45RA(+)CD45RO(-) naive Treg cells were lower in the NSTACS patients than in the chronic stable angina (CSA) and the chest pain syndrome (CPS) patients. However, the number of CD4(+)CD25(+)CD127(low)CD45RA(-) CD45RO(+) memory Treg cells was comparable in all of the groups. The frequency of CD4(+)CD25(+)CD127(low)CD45RO(-) CD45RA(+)CD31(+) recent thymic emigrant Treg cells and the T cell receptor excision circle content of purified Treg cells were lower in the NSTACS patients than in the CSA patients and the CPS controls. The spontaneous apoptosis of Treg cells (defined as CD4(+)CD25(+)CD127(low)annexinV(+)7-AAD(-)) was increased in the NSTACS patients compared with the CSA and CPS groups. Furthermore, oxidized LDL could induce Treg cell apoptosis, and the oxidized LDL levels were significantly higher in the NSTACS patients than in the CSA and CPS groups. In accordance with the altered Treg cell levels, the concentration of TNF-alpha was increased in the NSTACS patients, resulting in a decreased IL-10/TNF-alpha ratio. These findings indicate that the impaired thymic output of Treg cells and their enhanced susceptibility to apoptosis in the periphery were responsible for Treg cell defects observed in the NSTACS patients.