Normal human pregnancy results in maternal immune activation in the periphery and at the uteroplacental interface.
Normal human pregnancy results in maternal immune activation in the periphery and at the uteroplacental interface.
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DOI：
10.1371/journal.pone.0096723
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Kahn DA
中科院分区：
文献类型：
--
作者：
Loewendorf AI;Nguyen TA;Yesayan MN;Kahn DA
妊娠对人类免疫系统提出了独特的挑战：必须保护半同种异体胎儿免受母体免疫攻击，同时保持对病原体的免疫力。母胎耐受性的破坏可导致妊娠特异性疾病，对母亲和胎儿都具有潜在的高发病率和死亡率。各种免疫细胞类型可以介导这些功能，但在正常人妊娠外周和局部母体T细胞和调节性T细胞室的综合评价是缺乏的。在本病例对照研究中，我们将人类免疫学项目联盟提出的门控策略应用于健康妊娠晚期受试者的样本，并与健康非妊娠对照组进行比较。HLA-DR+和CD38+效应和效应记忆CD8 T细胞的比例在孕妇外周血中显著增加。利用一种新的技术，利用标准协议的优势，子宫内清洁剖宫产后，我们分离淋巴细胞居住在子宫胎盘界面（UPI）。在UPI，CD4和CD8 T细胞区室在很大程度上反映了外周血，除了HLA-DR+活化的T调节细胞的比例显著增加，与观察到的活化的CD8 T细胞数量的增加成正比。我们发现，冷冻保存和延迟的样品处理（> 12小时）降低了我们识别调节性T细胞亚群的能力。此外，该联盟提出的用于Treg鉴定的方法与活化的T细胞相比，未充分代表静息和细胞因子T细胞，因此使整个群体偏斜。更好地了解妊娠期间外周血和子宫胎盘界面免疫系统的变化对于治疗妊娠疾病（如先兆子痫和复发性流产）的进展至关重要。
Pregnancy poses a unique challenge to the human immune system: the semi-allogeneic fetus must be protected from maternal immune attack while immunity towards pathogens is maintained. Breakdown in maternal-fetal tolerance can lead to pregnancy-specific diseases with potentially high degrees of morbidity and mortality for both the mother and her fetus. Various immune cell-types could mediate these functions, but a comprehensive evaluation of the peripheral and local maternal T cell and regulatory T cell compartments in normal human pregnancy is lacking. In this case-control study, we apply the Human Immunology Project Consortium proposed gating strategies to samples from healthy 3rd trimester human subjects compared with healthy non-pregnant controls. The proportions of HLA-DR+ and CD38+ effector- and effector memory CD8 T cells are significantly increased in the peripheral blood of pregnant women. Utilizing a novel technique that takes advantage of the standard protocol for intrauterine cleanup after cesarean section, we isolate lymphocytes resident at the uteroplacental interface (UPI). At the UPI, the CD4 and CD8 T cell compartments largely mirror the peripheral blood, except that the proportion of HLA-DR+ activated T regulatory cells is significantly increased in direct proportion to an observed increase in the number of activated CD8 T cells. We find that cryopreservation and delayed sample processing (>12 hours) decreases our ability to identify regulatory T cell subsets. Further, the Consortium proposed method for Treg identification underrepresents Resting and Cytokine Tregs compared with Activated Tregs, thus skewing the entire population. Better understanding of the changes in the immune system during pregnancy in the peripheral blood and at the uteroplacental interface are essential for progress in treatment of pregnancy diseases such as pre-eclampsia and recurrent miscarriage.
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影响因子：
32.4
作者：
Fontenot, JD;Rasmussen, JP;Rudensky, AY
通讯作者：
Rudensky, AY
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作者：
Baecher-Allan, Clare;Wolf, Elizabeth;Haller, David A.
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Lanzavecchia, A
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作者：
Takahashi, T;Kuniyasu, Y;Sakaguchi, S
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Sakaguchi, S