During normal human pregnancy placental trophoblast serves as the continous cellular interface between the mother and developing fetus and comprises the greatest potential site of interaction with the maternal immune system. Conventional major histocompatibility complex encoded antigens (MHC) have not yet been detected on human villous trophoblast however it is conceivable that MHC antigens or other fetally encoded alloantigens may, in vivo, serve to stimulate a maternal immune reponse. Immunologic mechanisms responsible for the non-rejection of the fetal-placental unit during normal pregnancy, involving such alloantigens, may be distinct from those which occur during classical translantation reactions. Several lines of evidence implicate the importance during successful pregnancy of maternal immune responses directed at paternally encoded antigens or trophoblast specific antigens. The presence of anti-paternal lymphocytotoxic antibodles (LCTA) and maternal vs. paternal mixed lymphocyte blocking factors (MLRBF), in maternal serum have been correlated with successful pregnancy. We propose several experimental approaches to elucidate the immunological mechanisms involved in such immunoprotection of the fetal-placental unit. These are logical extensions of our clinical studies on diagnosis and treatment of women with repeated spontaneos abortions (RSA). It appears essential to examine trophoblast antigen expression during the first trimester of gestation since this is the time when immunologically mediated RSA usually occur. We intend to continue the characterization of cell surface antigen expression of chorionic villi (CV) obtained by chorionic villus sampling (CVS) by combining immunohistologic techniques with in situ hybridization which will allow detection of corresponding cellular mRNA. Examination of the specificity of maternal serum factors will be acheived by immunoprecipitation of labeled pooled CVS derived CV and lymphocyte membrane preparations with LCTA and MLRBF positive sera followed by polyacrylamide gel electrophoretic analysis. We will also examine the allostimulatory capacity of first trimester CV cells by conducting established in vitro cellular assays. These studies will represent the initial attempt to characterize CVS derived CV at the cell surface and molecular levels and the in vitro allostimulatory properties of first trimester placental cells.
