Placental trophoblast from successful human pregnancies expresses the tolerance signaling molecule, CD200 (OX-2)
Placental trophoblast from successful human pregnancies expresses the tolerance signaling molecule, CD200 (OX-2)
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DOI：
10.1034/j.1600-0897.2003.00086.x
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发表时间：
2003-09-01
影响因子：
3.6
通讯作者：
Gorczynski, RM
中科院分区：
文献类型：
--
作者：
Clark, DA;Keil, A;Gorczynski, RM
问题：在CBA x DBA/2小鼠模型中，Th 1细胞因子依赖性流产与流产过程开始前滋养层和蜕膜中CD 200（OX-2）“耐受”信号表达下调有关。流产可以通过给予可溶性CD 200来预防。CD 200在人类成功妊娠的滋养层细胞上表达吗？研究方法：由于在妊娠6周时流产过程开始之前的前三个月，人们不能容易地从成功的人类妊娠中大量获得滋养层，因此作为第一步，我们检查了从足月胎盘（即成功妊娠）分离的滋养层。用亲和柱分离CD 9（-）滋养层细胞，用PE-抗人CD 200单克隆抗体对细胞内细胞角蛋白和表面CD 200进行染色。从CD 9（+）和CD 9（-）细胞中提取mRNA，并通过逆转录-聚合酶链反应检测CD 200 mRNA。CD 9（-）胎盘细胞通过速度沉降法分离，并测试异基因人混合淋巴细胞培养物的CD 200依赖性抑制，其中细胞毒性T细胞（CTL）的产生和Th 1-> Th 2细胞因子产生的偏移被测量。流式细胞术显示CD 200（+）细胞角蛋白（+）中大型细胞群与滋养层细胞相容，细胞角蛋白（-）细胞的较小亚群以正常和高水平表达CD 200。中等规模的群体被证明在抑制CTL产生方面最有效，并引起Th 1-> Th 2细胞因子转变。结论：细胞角蛋白（+）胎盘滋养层细胞亚群表达具有生物活性的CD 200，能够改变母体免疫应答的Th 2> Th 1方向。CD 200（+）小细胞角蛋白（-）和中-小细胞角蛋白（-）胎盘细胞的两个群体仍有待鉴定。需要对妊娠早期选择性流产和自然流产组织进行核型分析研究。
PROBLEM: Th1 cytokine-dependent abortions in the CBA x DBA/2 mouse model have been linked to down-regulation of expression of the CD200 (OX-2) 'tolerance' signal on trophoblast and in decidua prior to onset of the abortion process. Abortions could be prevented by, administration of a soluble CD200. Is CD200 expressed on trophoblast in successful human pregnancy?METHOD OF STUDY: As one cannot easily obtain trophoblasts in large quantities from successful human pregnancies in the first trimester prior to the onset of the abortion process at 6 weeks gestation, we examined as a first step, trophoblast isolated from term placentae (i.e. successful pregnancies). CD9(-) trophoblasts were isolated by affinity column and stained for intracellular cytokeratin, and surface CD200 using PE-anti-human CD200 monoclonal antibody. mRNA was extracted from CD9(+) and CD9(-) cells and tested by reverse transcription-polymerase chain reaction for CD200 mRNA. CD9(-) placental cells were separated by velocity sedimentation and test for CD200-dependent suppression of an allogeneic human mixed lymphocyte culture where cytotoxic T cell (CTL) generation, and Th1 --> Th2 cytokine production shift were measured.RESULTS: CD9(-) but not CD9(+) placental cell populations contained cells with mRNA for CD200, both a normal length transcript and a truncated transcript. Flow cytometry showed a CD200(+) cytokeratin(+) moderate-to-large-sized cell population compatible with trophoblasts and a smaller subset of cytokeratin(-) cells that expressed CD200 at normal and at high levels. The moderate-sized population proved most potent at inhibiting CTL generation and caused a Th1 --> Th2 cytokine shift. These effects were blocked by monoclonal anti-CD200.CONCLUSIONS: A subpopulation of cytokeratin(+) placental trophoblasts express bioactive CD200 able to alter maternal immune responses in a favorable (Th2 > Th1) direction. Two populations of CD200(+) small- and medium-small-sized cytokeratin(-) placental cells remain to be identified. Studies of karyotyped first trimester elective termination and spontaneous miscarriage tissues are needed.