In vitro susceptibility of mouse placental trophoblast to cytotoxic effector cells.

The susceptibility of mouse placental cells to hyperimmune cell killing directed against paternal combined H-2 and non-H-2 antigens was investigated using [3H]uridine as a terminal label in an in vitro cell-mediated microcytotoxicity test. The stage of development of the conceptus from which the short-term placental cell monolayers were prepared determined their susceptibility to immune cell lysis. Cultures from whole placentae taken at 9 days post-coitum (p.c.) were not significantly affected whereas similar monolayers prepared at 10.5 days p.c. or later underwent extensive destruction. Embryonic fibroblasts were susceptible at all stages examined from 9-16 days p.c. The onset of susceptibility correlates with the reported appearance of H-2 antigens on the placenta during ontogeny. All cultures of dissected populations of 13-day p.c. placental spongiotrophoblast were susceptible but only 70% of those of labyrinthine trophoblast. It is suggested that of the two major trophoblastic components of the mouse placenta the spongiotrophoblast expresses antigens that render it vulnerable to maternal immune attack whilst the labyrinthine trophoblast is only weakly or non-antigenic, with the observed killing being due largely to contamination of these cultures by antigenic foetal mesenchymal elements. Since failure to express appropriate target antigens cannot be the reason for the in vivo survival of the spongiotrophoblast it must be presumed that some form of immunoregulatory mechanism(s) is responsible for the maintenance of the foeto-placental allograft.