Impaired thymic export and apoptosis contribute to regulatory T-cell defects in patients with chronic heart failure.
Impaired thymic export and apoptosis contribute to regulatory T-cell defects in patients with chronic heart failure.
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胸腺输出受损和细胞凋亡导致慢性心力衰竭患者的调节性 T 细胞缺陷
DOI：
10.1371/journal.pone.0024272
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Cheng X
中科院分区：
文献类型：
--
作者：
Tang TT;Zhu ZF;Wang J;Zhang WC;Tu X;Xiao H;Du XL;Xia JH;Dong NG;Su W;Xia N;Yan XX;Nie SF;Liu J;Zhou SF;Yao R;Xie JJ;Jevallee H;Wang X;Liao MY;Shi GP;Fu M;Liao YH;Cheng X
目的动物实验表明调节性T细胞(Treg细胞)在心室重构中起着有益的作用，我们以前的研究发现慢性心力衰竭(CHF)患者Treg细胞存在缺陷。然而，Treg细胞缺陷背后的机制仍然不清楚。我们在此试图阐明CHF患者Treg细胞缺陷的机制。方法与结果应用流式细胞仪分析表明，心力衰竭患者外周血中−+CD2 5+FOXP3+CD45RO、CD4+CD2 5+FOXP3+CD45RO+−记忆刺激(MTreg)细胞数量明显低于非心力衰竭对照组。此外，心力衰竭患者外周血中T细胞亚群比例(p<；0.01)、T细胞T细胞受体剪除环水平(p<；0.01)、−CD45RA+CD31+近期胸腺游走细胞(rte-Treg)频率(p<；0.01)均低于非心力衰竭对照组。Annexin-V和7-AAD联合染色显示，CHF患者外周血Treg细胞自发凋亡率增加，更容易被白介素2剥夺和CD95配体介导的细胞凋亡。此外，流式细胞仪和实时定量聚合酶链式反应分析显示，CHF患者纵隔淋巴结Treg细胞频率或心脏Foxp3表达均不高于非CHF对照组。结论CHF患者Treg细胞缺陷可能与胸腺新生Treg细胞输出量减少和外周细胞对细胞凋亡的易感性增加有关。
Objective Animal studies suggest that regulatory T (Treg) cells play a beneficial role in ventricular remodeling and our previous data have demonstrated defects of Treg cells in patients with chronic heart failure (CHF). However, the mechanisms behind Treg-cell defects remained unknown. We here sought to elucidate the mechanism of Treg-cell defects in CHF patients. Methods and Results We performed flow cytometry analysis and demonstrated reduced numbers of peripheral blood CD4+CD25+FOXP3+CD45RO−CD45RA+ naïve Treg (nTreg) cells and CD4+CD25+FOXP3+CD45RO+CD45RA− memory Treg (mTreg) cells in CHF patients as compared with non-CHF controls. Moreover, the nTreg/mTreg ratio (p<0.01), CD4+CD25+FOXP3+CD45RO− CD45RA+CD31+ recent thymic emigrant Treg cell (RTE-Treg) frequency (p<0.01), and T-cell receptor excision circle levels in Treg cells (p<0.01) were lower in CHF patients than in non-CHF controls. Combined annexin-V and 7-AAD staining showed that peripheral Treg cells from CHF patients exhibited increased spontaneous apoptosis and were more prone to interleukin (IL)-2 deprivation- and CD95 ligand-mediated apoptosis than those from non-CHF individuals. Furthermore, analyses by both flow cytometry and real-time polymerase chain reaction showed that Treg-cell frequency in the mediastinal lymph nodes or Foxp3 expression in hearts of CHF patients was no higher than that of the non-CHF controls. Conclusion Our data suggested that the Treg-cell defects of CHF patients were likely caused by decreased thymic output of nascent Treg cells and increased susceptibility to apoptosis in the periphery.
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DOI：
10.2353/ajpath.2010.090759
发表时间：
2010-05
期刊：
The American journal of pathology
影响因子：
--
作者：
Dobaczewski M;Xia Y;Bujak M;Gonzalez-Quesada C;Frangogiannis NG
通讯作者：
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DOI：
10.1084/jem.20060772
发表时间：
2006-07-10
期刊：
The Journal of experimental medicine
影响因子：
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作者：
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影响因子：
82.9
作者：
Ait-Oufella, H;Salomon, BL;Mallat, Z
通讯作者：
Mallat, Z
急性冠脉综合征患者Th17/Treg失衡
影响因子：
8.6
作者：
Cheng, Xiang;Yu, Xian;Liao, Yu-hua
通讯作者：
Liao, Yu-hua
影响因子：
4.6
作者：
Kleinbongard, Petra;Schulz, Rainer;Heusch, Gerd
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