The Role of Placental Fas Ligand in Maintaining Immune Privilege at Maternal-fetal Interfaces

It is now recognized that immunosuppressive factors synthesized by placenta may play a critical role in the maintenance of pregnancy. Over the last several years our group and others have formulated a hypothesis that trophoblast Fas ligand (FasL) plays an important role in maintaining fetal immune privilege in human pregnancy by actively promoting apoptosis (programmed cell death) of activated maternal lymphocytes bearing Fas (i.e., the FasL receptor). This review initially provides background information and updates aspects of the Fas/FasL signaling system, including the role of caspases and molecules recruited to the Fasl/Fas signaling complex and the revised functions ascribed to membrane and soluble forms of FasL. Information is then presented concerning the role of FasL at immune-privileged sites including the eye and testis. Pathways through which the placenta and tumors avoid may avoid immune clearance vis-à-vis the FasL/Fas signaling cascade are described. A model is then presented through which FasL production by human syncytiotrophoblasts and extravillous trophoblasts may protect the fetus against the cytolytic actions of activated Fas-bearing maternal lymphocytes in the intervillous space and in the placental bed, respectively. We conclude with a review of studies in support this model that specifically demonstrate trophoblast expression of FasL and identify potential lymphocyte targets (i.e., Fas-expressing maternal immune cells) of trophoblast FasL.