Petroff Margaret G, Chen Lieping, Phillips Teresa A, Azzola Dagmar, Sedlmayr Peter, Hunt Joan S
Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City 66160, USA.
Biol Reprod. 2003 May;68(5):1496-504. doi: 10.1095/biolreprod.102.010058. Epub 2002 Nov 27.
The human placenta utilizes both active and passive mechanisms to evade rejection by the maternal immune system. We investigated the pattern of expression of the B7 family of immunomodulatory molecules B7-H1 (PD-L1), B7-2 (CD86), and B7-1 (CD80) at the term maternal-fetal interface. Northern blot and reverse transcription-polymerase chain reaction (RT-PCR) analyses showed that B7-H1 mRNA is abundant in term placenta and that cytotrophoblasts are sources of this message. Immunohistochemistry demonstrated that B7-H1 is constitutively expressed by the syncytiotrophoblast and by extravillous cytotrophoblasts, both of which are juxtaposed to maternal blood and tissue. By contrast, placental stromal cells, including macrophages, lacked the protein. Expression of B7-H1 protein was low in first-trimester placenta compared to second- and third-trimester tissue (P < 0.05) and was enhanced in cultured cytotrophoblasts by treatment with either interferon-gamma or epidermal growth factor (P < 0.05), suggesting that one or both of these mediators regulates B7-H1 expression in the placenta. RT-PCR and immunofluorescence analysis of term placental tissue revealed different patterns of expression of the immunostimulatory protein, B7-2. In contrast to B7-H1, B7-2 mRNA and protein were absent in cytotrophoblast cells but present in maternal macrophages and some fetal macrophages. The B7-1 mRNA and protein were absent at the maternal-fetal interface. These studies document expression of the B7 family proteins at the maternal-fetal interface and demonstrate that B7-H1 is positioned such that it could facilitate protection of fetal cells against activated maternal leukocytes. Conversely, B7-2 was absent on trophoblasts and was appropriately localized to fetal and maternal macrophages, which may participate in antigen presentation.
人类胎盘利用主动和被动机制来逃避母体免疫系统的排斥。我们研究了免疫调节分子B7家族的B7-H1（PD-L1）、B7-2（CD86）和B7-1（CD80）在足月母胎界面的表达模式。Northern印迹和逆转录-聚合酶链反应（RT-PCR）分析表明，B7-H1 mRNA在足月胎盘中含量丰富，细胞滋养层细胞是该信息的来源。免疫组织化学显示，B7-H1由合体滋养层细胞和绒毛外细胞滋养层细胞组成性表达，这两种细胞均与母体血液和组织相邻。相比之下，包括巨噬细胞在内的胎盘基质细胞缺乏该蛋白。与孕中期和孕晚期组织相比，孕早期胎盘B7-H1蛋白表达较低（P < 0.05），用干扰素-γ或表皮生长因子处理培养的细胞滋养层细胞后，B7-H1蛋白表达增强（P < 0.05），这表明这些介质中的一种或两种调节胎盘中B7-H1的表达。足月胎盘组织的RT-PCR和免疫荧光分析揭示了免疫刺激蛋白B7-2的不同表达模式。与B7-H1不同，细胞滋养层细胞中不存在B7-2 mRNA和蛋白，但在母体巨噬细胞和一些胎儿巨噬细胞中存在。母胎界面不存在B7-1 mRNA和蛋白。这些研究记录了B7家族蛋白在母胎界面的表达，并证明B7-H1的定位使其能够促进胎儿细胞免受活化母体白细胞的攻击。相反，滋养层细胞上不存在B7-2，其在胎儿和母体巨噬细胞中定位适当，这可能参与抗原呈递。
