Differentiation of ICOS+ and ICOS− recent thymic emigrant regulatory T cells (RTE Tregs) during normal pregnancy, pre‐eclampsia and HELLP syndrome
Differentiation of ICOS+ and ICOS− recent thymic emigrant regulatory T cells (RTE Tregs) during normal pregnancy, pre‐eclampsia and HELLP syndrome
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DOI：
10.1111/cei.12693
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发表时间：
2016-01
影响因子：
4.6
通讯作者：
M. Wagner;M. Jöst;J. Spratte;M. Schaier;K. Mahnke;S. Meuer;M. Zeier;A. Steinborn
中科院分区：
文献类型：
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作者：
M. Wagner;M. Jöst;J. Spratte;M. Schaier;K. Mahnke;S. Meuer;M. Zeier;A. Steinborn
人类胸腺产生两种不同的自然产生的调节性T细胞(NTregs)亚群，由它们表达的可诱导共刺激(ICOS)分子定义。为了研究ICOS+和ICOS−CD45RA+CD31+新近胸腺移居T细胞在正常妊娠和有先兆子痫或溶血时肝酶升高的低血小板综合征中的分化情况，我们用六色流式细胞术分析了ICOS+和ICOS−细胞池中CD45RA+CD31+−成熟幼稚(MN)Tregs、CD45RA−CD31+和CD45RA−CD31−Memory Treg的组成变化。从妊娠开始到足月，我们观察到ICOS+和ICOS−CD45RA+CD31+RTE强烈分化为CD45RA+CD31−MN Tregs，而不是CD45RA−CD31−记忆Tregs。在妊娠结束时，自然足月分娩的开始与ICOS+CD45RA、−、CD31、−记忆树显著受损有关。在子痫前期患者中，ICOS+和ICOS−CD45RA+CD31+RTE树向CD45RA−CD31+记忆树分化明显增加，其中向CD45RA−CD31−记忆树的分化不足部分被ICOS+和ICOS−CD45RA+CD31−MN树向CD45RA−CD31−记忆树的分化增强所部分取代。在HELLP综合征患者中，CD45RA−CD31−MN Treg的这种交替分化似乎被夸大了，并可能恢复了磁隔离的ICos+和ICos−Treg的抑制活性，这两种抑制活性在先兆子痫患者中显著降低，但在HELLP综合征患者中不明显。因此，我们的研究结果表明，ICOS+和ICOS−CD45RA+CD31+RTE Tregs的正常分化确保了健康的妊娠过程，而它们的分化障碍与先兆子痫和HELLP综合征的发生有关。
Two different subsets of naturally occurring regulatory T cells (nTregs), defined by their expression of the inducible co‐stimulatory (ICOS) molecule, are produced by the human thymus. To examine the differentiation of ICOS+ and ICOS−CD45RA+CD31+ recent thymic emigrant (RTE) Tregs during normal pregnancy and in the presence of pre‐eclampsia or haemolysis elevated liver enzymes low platelet (HELLP)‐syndrome, we used six‐colour flow cytometric analysis to determine the changes in the composition of the ICOS+ and ICOS− Treg pools with CD45RA+CD31+ RTE Tregs, CD45RA+CD31− mature naive (MN) Tregs, CD45RA−CD31+ and CD45RA−CD31− memory Tregs. With the beginning of pregnancy until term, we observed a strong differentiation of both ICOS+ and ICOS−CD45RA+CD31+ RTE, but not CD45RA+CD31− MN Tregs, into CD45RA−CD31− memory Tregs. At the end of pregnancy, the onset of spontaneous term labour was associated with a significant breakdown of ICOS+CD45RA−CD31− memory Tregs. However, in the presence of pre‐eclampsia, there was a significantly increased differentiation of ICOS+ and ICOS−CD45RA+CD31+ RTE Tregs into CD45RA−CD31+ memory Tregs, wherein the lacking differentiation into CD45RA−CD31− memory Tregs was partially replaced by the increased differentiation of ICOS+ and ICOS−CD45RA+CD31− MN Tregs into CD45RA−CD31− memory Tregs. In patients with HELLP syndrome, this alternatively increased differentiation of CD45RA−CD31− MN Tregs seemed to be exaggerated, and presumably restored the suppressive activity of magnetically isolated ICOS+ and ICOS− Tregs, which were shown to be significantly less suppressive in pre‐eclampsia patients, but not in HELLP syndrome patients. Hence, our findings propose that the regular differentiation of both ICOS+ and ICOS−CD45RA+CD31+ RTE Tregs ensures a healthy pregnancy course, while their disturbed differentiation is associated with the occurrence of pre‐eclampsia and HELLP syndrome.