August C S, Cox S T, Naughton M A
J Clin Invest. 1979 Mar;63(3):428-36. doi: 10.1172/JCI109319.
Cultured choriocarcinoma (Be Wo) cells exist that share many of the morphologic and bio-synthetic properties of normal human trophoblasts. In an attempt to develop a model for the immunologic relationship between a sensitized mother and fetus, we mixed Be Wo cells with mitogen-activated cytotoxic lymphocytes in vitro. Be Wo cells were resistant to the cytolytic effects of the activated lymphocytes despite 24-h exposure and intimate cell-to-cell contact as determined by microscopy. Control target cells, a line of human hepatoma cells, were readily destroyed. Cytotoxicity was measured by determining residual radioactivity of [(3)H]thymidine-labeled target cells after exposure to activated lymphocytes. Employing the quantitative assay, we confirmed the morphologic results and showed that Be Wo and a number of other choriocarcinoma cell lines were resistant to the cytotoxic effects of lymphocytes activated by phytohemagglutinin, pokeweed mitogen, and allogeneic cells in mixed lymphocyte cultures. Moreover, Be Wo cells were resistant to injury over a wide range of killer to target cell ratios. Significant killing of the Be Wo cells occurred only after prolonged exposure (48 and 72 h) to the activated lymphocytes. We suggest that one mechanism that may assist the fetus (or a choriocarcinoma) in its immunologic survival is the intrinsic resistance of trophoblast cells to lymphocyte-mediated cytotoxicity.
培养的绒毛膜癌细胞(Be Wo细胞系)具有许多与正常人滋养层细胞相同的形态学和生物合成特性。为了建立一个致敏母亲与胎儿之间免疫关系的模型,我们在体外将Be Wo细胞与有丝分裂原激活的细胞毒性淋巴细胞混合。通过显微镜观察发现,尽管暴露24小时且细胞间紧密接触,但Be Wo细胞对激活的淋巴细胞的细胞溶解作用具有抗性。作为对照的靶细胞,一种人肝癌细胞系,则很容易被破坏。细胞毒性通过测定暴露于激活淋巴细胞后[³H]胸腺嘧啶标记的靶细胞的残余放射性来衡量。采用定量测定法,我们证实了形态学结果,并表明Be Wo细胞系和其他一些绒毛膜癌细胞系对植物血凝素、商陆有丝分裂原以及混合淋巴细胞培养中的同种异体细胞激活的淋巴细胞的细胞毒性作用具有抗性。此外,在很宽的杀伤细胞与靶细胞比例范围内,Be Wo细胞均具有抗性。只有在长时间(48小时和72小时)暴露于激活的淋巴细胞后,Be Wo细胞才会出现明显的杀伤。我们认为,滋养层细胞对淋巴细胞介导的细胞毒性的内在抗性可能是帮助胎儿(或绒毛膜癌)实现免疫存活的一种机制。