Impaired circulating CD4+ LAP+ regulatory T cells in patients with acute coronary syndrome and its mechanistic study.

Impaired circulating CD4+ LAP+ regulatory T cells in patients with acute coronary syndrome and its mechanistic study.
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DOI:
10.1371/journal.pone.0088775
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Zeng QT
Zeng QT
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zhu ZF;Meng K;Zhong YC;Qi L;Mao XB;Yu KW;Zhang W;Zhu PF;Ren ZP;Wu BW;Ji QW;Wang X;Zeng QT

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CD4+潜伏期相关肽(LAP)+调节性T细胞(Tregs)是一种新发现的人类T细胞亚群,这些细胞在急性冠脉综合征(ACS)患者中的作用尚未被探索。我们旨在探讨CD4+LAP+ treg的循环频率和功能是否在ACS中存在缺陷。111例ACS患者(急性心肌梗死和不稳定型心绞痛)和117例对照患者纳入研究。对照组为慢性稳定型心绞痛(CSA)和胸痛综合征(CPS)。流式细胞术检测CD4+LAP+ Tregs循环频率及CD4+ T细胞跨膜糖蛋白- a重复优势序列(GARP)表达。采用胸腺嘧啶摄取法检测CD4+LAP+ Tregs的功能。ELISA法检测血清白细胞介素-10 (IL-10)和转化生长因子-β蛋白(TGF-β)水平,实时聚合酶链反应法检测外周血单个核细胞(PBMCs) GARP mRNA表达。我们发现ACS患者循环CD4+LAP+ Tregs的频率明显较低,与对照组相比,这些细胞的功能降低。ACS患者CD4+ T细胞GARP表达及血清TGF-β水平均低于对照组。两组患者血清IL-10水平相似。一种新的调节性T细胞亚群,定义为CD4+LAP+ T细胞在ACS患者中存在缺陷。
CD4+ latency-associated peptide (LAP)+ regulatory T cells (Tregs) are a newly discovered T cell subset in humans and the role of these cells in patients with acute coronary syndrome (ACS) has not been explored. We designed to investigate whether circulating frequency and function of CD4+LAP+ Tregs are defective in ACS. One hundred eleven ACS patients (acute myocardial infarction and unstable angina) and 117 control patients were enrolled in the study. The control patients consisted of chronic stable angina (CSA) and chest pain syndrome (CPS). The frequencies of circulating CD4+LAP+ Tregs and the expression of the transmembrane protein glycoprotein-A repetitions predominant (GARP) on CD4+ T cells were determined by flow cytometry. The function of CD4+LAP+ Tregs was detected using thymidine uptake. Serum interleukin-10 (IL-10) and transforming growth factor-β protein (TGF-β) levels were detected using ELISA and expression of GARP mRNA in peripheral blood mononuclear cells (PBMCs) was measured by real time-polymerase chain reaction. We found ACS patients had a significantly lower frequency of circulating CD4+LAP+ Tregs, and the function of these cells was reduced compared to controls. The expression of GARP in CD4+ T cells and the serum levels of TGF-β in ACS patients were lower than those of control patients. The serum levels of IL-10 were similar between the two cohorts. A novel regulatory T cell subset, defined as CD4+LAP+ T cells is defective in ACS patients.
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