Immunosuppressive properties of human placenta: study of supernatants from short-term syncytiotrophoblast cultures

Abstract

Using collagenase and mechanical treatment to attempt to eliminate cellular contamination such as macrophages and decidual cells, trophoblast enriched cell suspensions were isolated from the human placenta. With a view to assessing the role of trophoblast in impairing maternal rejection of the fetus, supernatants (SP1 4) were prepared from these placental cells after short-term culture (4 h). The immunosuppressive activity of these supernatants was studied following application to mitogen-stimulated human lymphocyte cultures and mixed lymphocyte cultures. In both cases a reproducible inhibition was observed. The ability of these substances to induce a non-specific inhibitory effect was ascertained by observing mouse lymphocyte responses to mitogens or alloantigens. To gain further insight into in vivo fetal protection against anti-paternal cells, we also examined the effects of SP1 4 on CTL generation. It was found not only that CTL generation was markedly depressed but also that SP1 4 drastically impaired cell-mediated lympholysis at the effector level. To characterize the factors involved in our observations, SP1 4 was subjected to dialysis and to chromatography. In the first case, it was found that these factors were not amenable to dialysis. In the second case, we obtained on an Ultrogel AcA 44 column two fractions with immunosuppressive activity. Following our previous work on human syncytiotrophoblast, we analyzed only the low molecular weight inhibitory fraction, which was chromatographed again on Ultrogel AcA 202. The molecular weight of the immunosuppressive factor(s) was estimated to be around 3.5 kDa. We postulate that human trophoblast releases soluble factors around the fetus which may act to protect it against maternal immunological rejection.