Zuckermann F A, Head J R
Graduate Studies Program in Immunology, University of Texas Health Science Center, Dallas 75235.
J Immunol. 1987 Nov 1;139(9):2856-64.
Research on the mechanisms of nonrejection of the fetoplacental allograft has focused on the tissues composing the fetomaternal interface, of which the placental trophoblast, the tissue directly confronting the maternal environment, is considered a prime candidate responsible for the survival of the fetus. We recently developed a method for isolating murine trophoblast, and found that a proportion of trophoblast cells from mature placentas, cultured for 2 days, express class I antigens on their surface, and this expression can be enhanced in vitro by interferon-alpha/beta (IFN-alpha/beta). In the present study, it was determined that cultured trophoblast cells from day 14 placentas were resistant to allospecific cytotoxic T lymphocytes (allo-CTL), while being susceptible to alloantibody and complement-mediated lysis. The trophoblast cells remained resistant to allo-CTL-mediated lysis despite IFN-mediated enhanced expression of class I H-2 antigens on their surface and the addition of phytohemagglutinin into the assay. Inhibition of protein synthesis also had no effect. In contrast, fetal fibroblasts, isolated from the same conceptuses, were readily susceptible to allo-CTL-mediated lysis. That the trophoblast cells do interact with the effector cells was shown by their ability to specifically inhibit the lysis of tumor target cells in a dose-dependent manner. Additionally, trophoblast culture supernatants did not inhibit the lytic activity of allo-CTL, even when concentrated 10- to 25-fold, indicating that a soluble suppressor factor was not inactivating the effector cells. These results suggest that trophoblast cells have a protein synthesis-independent mechanism of resistance to lysis by allo-CTL, which could play an important role in protecting the fetoplacental allograft from maternal immune rejection.
对胎盘同种异体移植不被排斥机制的研究主要集中在构成母胎界面的组织上，其中胎盘滋养层是直接面对母体环境的组织，被认为是胎儿存活的主要负责因素。我们最近开发了一种分离小鼠滋养层的方法，发现从成熟胎盘分离并培养2天的一部分滋养层细胞在其表面表达I类抗原，并且这种表达可在体外通过α/β干扰素（IFN-α/β）增强。在本研究中，确定来自第14天胎盘的培养滋养层细胞对同种异体特异性细胞毒性T淋巴细胞（allo-CTL）具有抗性，而对同种异体抗体和补体介导的裂解敏感。尽管IFN介导其表面I类H-2抗原表达增强且在试验中添加了植物血凝素，但滋养层细胞仍对allo-CTL介导的裂解具有抗性。蛋白质合成的抑制也没有效果。相比之下，从同一胚胎分离的胎儿成纤维细胞很容易受到allo-CTL介导的裂解。滋养层细胞能够以剂量依赖性方式特异性抑制肿瘤靶细胞的裂解，这表明它们确实与效应细胞相互作用。此外，滋养层培养上清液即使浓缩10至25倍也不会抑制allo-CTL的裂解活性，这表明可溶性抑制因子不会使效应细胞失活。这些结果表明，滋养层细胞具有一种不依赖蛋白质合成的机制来抵抗allo-CTL的裂解，这可能在保护胎盘同种异体移植免受母体免疫排斥中起重要作用。
