The Sensitivity of Placental Trophoblast Cells to Intraplacental and Allogeneic Cytotoxic Lymphocytes

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Abstract
The NK‐susceptibility of trophoblast cells to allogeneic and autologous intraplacental natural killer (NK), antibody‐dependent (K), and mitogen‐induced cell‐mediated cytotoxicity was studied, using untreated and neuraminidase‐treated trophoblast cells from normal, full‐term deliveries. The work was preceded by systematic studies of placental cell separation and labelling techniques, and the effects of these techniques on the NK target, K562. The results indicated that maternal NK cells are present among intraplacental lymphocytes, but that their activity is lower than that of peripheral blood lymphocytes and they are not stimulated by interferon to the same extent as peripheral blood lymphocytes (PBL). Trophoblast cells were rarely susceptible to allogeneic NK cells, with low cytotoxicity at high effector‐target cell ratios in only two of five experiments. Interferon (IF)‐boosted NK cells mediated some cytolysis of trophoblasts in three of four experiments, but high effector/target cell ratios were also required for the effect to be observed. The trophoblast cells could be lysed, however, by K cells and lectin‐induced cytotoxicity. Removal of surface sialic acid by neuraminidase treatment of the trophoblast cells had little effect on the susceptibility of these cells to unstimulated NK cells (one of four experiments), but resulted in susceptibility to IF‐boosted NK cells in four of four experiments. Normal trophoblast cells did not compete in IF‐NK(K562) assays and neuraminidase‐treated cells competed weakly in only one of three such experiments, indicating that the NK “target structure” is only weakly expressed on human trophoblast cells. Intraplacental lymphocytes lysed autologous trophoblast cells to a lower extent than allogeneic PBL. This lysis was markedly increased if antibody against the target cells was present in the assay. These data indicate that a) the trophoblast cell is susceptible to maternal cell‐mediated lysis by several mechanisms that could potentially be activated in vivo, b) NK cells are present in the intraplacental lymphocyte pool, and c) the access of NK cells and interferon activated NK cells to the NK cell target structure is blocked by cell surface sialic acid residues. This target structure may be similar to that found on other susceptible cells, and in similarity to the tumor—NK interaction, the cell surface sialic acid is ineffective in blocking cytotoxicity if the appropriate antibody is present. Assuming NK cells mediate ADCC, this indicates that sialic acid does not mask the target site of the lytic molecule. These data are relevant to the understanding of the NK– target interaction in a situation where it is known that the target is nonself.