Abstract
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 Fast 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 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-a-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.
