Sabapatha Anuradha, Gercel-Taylor Cicek, Taylor Douglas D
Department of Obstetrics, Gynecology, and Women's Health, University of Louisville School of Medicine, Louisville, KY 40202, USA.
Am J Reprod Immunol. 2006 Nov-Dec;56(5-6):345-55. doi: 10.1111/j.1600-0897.2006.00435.x.
One immunoregulatory pathway receiving little attention is placental exosome release. In normal pregnancy, as factors linked with early immunomodulation decline, placental exosomes become critical in modulating T-cell activation, suppressing effector T cells by enhancing lymphocyte apoptosis and CD3-zeta loss.
Placental exosomes were specifically isolated from the maternal peripheral circulation by a chromatographic/immunosorbent procedure. Exosomal suppression of T-cell signaling molecules on unfractionated T cells and T subsets was analyzed by Western immunoblot. The role of Fas ligand (FasL) was defined by use of Fas-blocking antibody.
While exosomes of lymphoid origin could be demonstrated in all women, placenta-derived exosomes were only identified in pregnant patients. Placental exosomes suppressed T-cell expression of CD3-zeta and JAK3, while inducing SOCS-2. This downregulation of CD3-zeta was partially reversed by pre-incubating T cells with ZB4 antibody. Using T subsets, the level of CD3-zeta on CD8+ cells was inhibited 1.43-fold more than in CD4+ cells. On CD4+ CD25+ cells, CD3-zeta was not significantly inhibited.
Placental exosomes suppressed T-cell signaling components; however, while exosomal FasL is an important contributor, it does not appear to be the sole mediator. The additional expression of PD-L1 may explain immunoregulatory consequences of exosomes with low or absent FasL.
一个很少受到关注的免疫调节途径是胎盘外泌体的释放。在正常妊娠中，随着与早期免疫调节相关的因子减少，胎盘外泌体在调节T细胞活化方面变得至关重要，通过增强淋巴细胞凋亡和CD3-ζ丢失来抑制效应T细胞。
通过色谱/免疫吸附程序从母体外周循环中特异性分离胎盘外泌体。通过蛋白质免疫印迹分析外泌体对未分级T细胞和T细胞亚群上T细胞信号分子的抑制作用。使用Fas阻断抗体确定Fas配体（FasL）的作用。
虽然在所有女性中都可以检测到淋巴来源的外泌体，但仅在孕妇中鉴定出胎盘来源的外泌体。胎盘外泌体抑制T细胞中CD3-ζ和JAK3的表达，同时诱导SOCS-2。用ZB4抗体预孵育T细胞可部分逆转CD3-ζ的这种下调。使用T细胞亚群，CD8+细胞上CD3-ζ的水平比CD4+细胞中的抑制程度高1.43倍。在CD4+CD25+细胞上，CD3-ζ没有受到明显抑制。
胎盘外泌体抑制T细胞信号成分；然而，虽然外泌体FasL是一个重要因素，但它似乎不是唯一的介质。PD-L1的额外表达可能解释了FasL含量低或缺乏的外泌体的免疫调节后果。
