Trophoblast modulation of maternal allogeneic recognition

Abstract

Human syncytiotrophoblast cell membranes prepared by differential ultracentrifugation were extracted with 3 M KCl, solubilized in 1% deoxycholate, and chromatographically separated into two peaks by passage through a column of Bio-Gel P-200. Previous reports from this laboratory have shown that the first peak (PI) is serologically the same as a group of trophoblast membrane antigens tentatively designated as TA1. Microgram amounts of P1 protein were found to completely inhibit the mixed lymphocyte culture (MLC) reaction but had no suppressive effect on lymphocyte responses to the lectins phytohemagglutinin or pokeweed mitogen. Control P1 membrane fractions identically prepared from human erythrocytes and liver powder had no inhibitory effects on either MLC reactions or lymphocyte responses to mitogens. Dose response experiments with P1 from 10 different placentae showed total inhibition of MLC by all preparations when used between 25 and 50 microgram/0.2-ml MLC mixture, but some P1 fractions inhibited significantly at much lower concentrations. Timed experiments revealed that MLC suppression was maximal when P1 was added within 12 hr after culture initiation and that no effect could be found with addition after 48 hr. We have previously shown that TA1 is a lymphocyte product of allogeneic responses, and the present results indicate that P1 proteins are themselves involved in the biology of lymphocyte responses to allogeneic cells. Pregnancy is one of the few natural circumstances in which a mixing of allogeneic cells occurs in vivo, and the presence of P1 proteins at the operational interface in the host-parasite relationship of human pregnancy suggests that this trophoblast membrane constituent is involved in the modulation of maternal allogeneic responses.