High-progesterone environment preserves T cell competency by evading glucocorticoid effects on immune regulation.
High-progesterone environment preserves T cell competency by evading glucocorticoid effects on immune regulation.
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DOI：
10.3389/fimmu.2022.1000728
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发表时间：
2022
影响因子：
7.3
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中科院分区：
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孕激素（P4）和糖皮质激素（GC）在母亲接受和维持半同种异体胎儿的免疫调节中起着至关重要的作用。P4浓度在怀孕期间增加，并且在胎盘中变得比在其他外周组织中高得多，其中皮质醇（COR）（最丰富的GC和强免疫抑制剂）的浓度在身体的其余部分保持均匀。在这里，我们通过与COR比较，评估了高P4环境对妊娠免疫力的影响。孕妇分娩后外周血中幼稚T细胞比例短暂升高，1个月后下降。在P4存在的情况下，用超抗原中毒性休克综合征-1（TSST-1）刺激的T细胞保持在幼稚状态，无论COR是否存在，反应性T细胞都不能存活。在没有T细胞受体（TCR）刺激的情况下用P4处理T细胞短暂抑制T细胞活化和增殖，而如果在刺激之前没有给予P4，则水平保持不变。使用hu-PBL-NOG-hIL-4-Tg小鼠的移植和对特异性抗原的应答的比较显示，P4预处理的淋巴细胞保留了CD 62 L表达并有效地移植到脾脏中。此外，它们产生抗原特异性抗体，而COR预处理的淋巴细胞没有。这些结果表明，高P4环境抑制T细胞活化并诱导T细胞迁移到淋巴组织中，在那里它们保持产生抗病原体抗体的能力，而COR不保留T细胞功能。该机制可能对于维持妊娠期间非胎儿特异性T细胞功能至关重要。
Progesterone (P4) and glucocorticoid (GC) play crucial roles in the immunoregulation of a mother to accept and maintain a semi-allogenic fetus. P4 concentration increases during pregnancy and becomes much higher in the placenta than in the other peripheral tissues, wherein the concentration of cortisol (COR), the most abundant GC and a strong immunosuppressor, remains uniform throughout the rest of the body. Here, we evaluated the effect of a high-P4 environment on pregnant immunity by comparing it with COR. Naïve T cell proportion increased transiently in peripheral blood of pregnant women just after delivery and decreased after one month. T cells stimulated with superantigen toxic-shock-syndrome-1 (TSST-1) in the presence of P4 stayed in the naïve state and did not increase, irrespective of the presence of COR, and reactive T cells could not survive. Treatment of T cells with P4 without T cell receptor (TCR) stimulation transiently suppressed T cell activation and proliferation, whereas the levels remain unaltered if P4 was not given before stimulation. Comparison of the engraftment and response against specific antigens using hu-PBL-NOG-hIL-4-Tg mice showed that P4-pretreated lymphocytes preserved CD62L expression and engrafted effectively in the spleen. Moreover, they produced antigen-specific antibodies, whereas COR-pretreated lymphocytes did not. These results suggest that a high-P4 environment suppresses T cell activation and induces T cell migration into lymphoid tissues, where they maintain the ability to produce anti-pathogen antibodies, whereas COR does not preserve T cell function. The mechanism may be pivotal in maintaining non-fetus-specific T cell function in pregnancy.