Altered status of CD4+CD25+ regulatory T cells in patients with acute coronary syndromes
Altered status of CD4+CD25+ regulatory T cells in patients with acute coronary syndromes
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DOI：
10.1093/eurheartj/ehl222
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发表时间：
2006-11-01
影响因子：
39.3
通讯作者：
George, Jacob
中科院分区：
文献类型：
--
作者：
Mor, Adi;Luboshits, Galia;George, Jacob
目的大量证据支持先天免疫和适应性免疫在动脉粥样硬化斑块的进展和不稳定中的作用。自然发生的CD4(+)CD25（+）调节性T细胞（Tregs）是一种能够抑制实验性自身免疫性疾病进展的淋巴细胞亚群。我们假设急性冠脉综合征（ACS）患者外周血treg数量和功能紊乱。方法和结果采用流式细胞仪（FACS）检测外周血treg细胞CD4和CD25标记抗体。通过建立三细胞培养，将纯化的Tregs与辐照的抗原呈递细胞和抗cd3激活的应答T细胞孵育，检测Tregs的功能抑制特性。通过胸腺嘧啶掺入评价氧化LDL （oxLDL）存在或不存在时的增殖。检测所有受试者Tregs的主要转录调控因子foxp3的mRNA和蛋白含量。ACS患者与稳定型心绞痛患者和冠状动脉正常患者相比，外周血treg数量明显减少。此外，oxLDL诱导ACS患者Treg数量的减少更为显著。ACS患者的Tregs显著受损，因为它们抑制CD4(+)CD25(-) t细胞增殖的能力减弱。从ACS患者获得的纯化treg中foxp3 mRNA和蛋白含量显著降低。结论在ACS患者中，自然发生的CD4(+)CD25(+) Treg数量减少，其功能特性受到损害。这些发现可能有助于理解导致ACS患者斑块相关t细胞活化的机制。
Aims Considerable evidence supports the role of innate and adaptive immunity in the progression and destabilization of the atheromatous plaque. Naturally occurring CD4(+)CD25(+) regulatory T cells (Tregs) are a subpopulation of lymphocytes that are capable of suppressing the progression of experimental autoimmune disorders. We have hypothesized that peripheral numbers and function of Tregs would be deranged in patients with acute coronary syndromes (ACS).Methods and results Peripheral numbers of Tregs were evaluated by FACS employing labelled antibodies to CD4 and CD25. Functional suppressive properties of Tregs were assayed by establishing a triple-cell culture in which purified Tregs were incubated with irradiated antigen-presenting cells and anti-CD3-activated responder T cells. Proliferation in the presence or absence of oxidized LDL (oxLDL) was evaluated by thymidine incorporation. mRNA and protein content of foxp3, a master transcriptional regulator of Tregs, were determined for all subjects. Patients with ACS exhibited significantly reduced numbers of peripheral Tregs as compared with patients with stable angina and normal coronary artery subjects. Moreover, oxLDL induced a more profound reduction in Treg numbers in patients with ACS. Tregs in ACS patients were significantly compromised as their ability to suppress responder CD4(+)CD25(-) T-cell proliferation was attenuated. mRNA and protein content of foxp3 were significantly reduced in purified Tregs obtained from patients with ACS.Conclusion In patients with ACS, naturally occurring CD4(+)CD25(+) Treg numbers are reduced and their functional properties compromised. These findings may aid in understanding the mechanisms leading to culprit plaque associated T-cell activation in patients with ACS.