EXPRESSION OF FAS LIGAND BY HUMAN CYTOTROPHOBLASTS - IMPLICATIONS IN PLACENTATION AND FETAL SURVIVAL

Recent data indicated that local production of Fas ligand (Fast) by ce lls of the eye and testis may confer immune tolerance at these sites. In the present study, we examined the in vivo and in vitro patterns of expression of Fast in the human placenta to provide a potential mecha nism through which the fetus is afforded protection against the cytoly tic actions of lymphocytes present within maternal decidua across gest ation. Immunohistochemical staining of first trimester human placental tissue sections revealed the presence of FasL in cytotrophoblasts in free floating villi anchoring villi, and cytotrophoblastic islands. Fa st staining was also pronounced in syncytiotrophoblasts of term placen ta indicating that Fast expression is maintained across gestation. Mul tiple molecular forms of Fast, suggestive of altered patterns of glyco sylation, were detected in extracts of term placenta, amnion and chori on by Western blotting. In addition, in vitro expression of Fast was d emonstrated to increase 2 to 3-fold during differentiation of primary cultures of cytotrophoblasts isolated from human term placentas. Local production of Fast by human cytotrophoblasts provides a mechanism thr ough which cytotrophoblasts may induce immune tolerance and self-regul ate survival during invasion and subsequent placentation.