Fas‐Fas Ligand System‐Induced Apoptosis in Human Placenta and Gestational Trophoblastic Disease

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Abstract
PROBLEM: The low frequency of maternal immune responses to paternally inherited fetal antigens raises the following question: What regulates the immunobiology of pregnancy? Data suggest that this state is the result of peripheral immune‐tolerance, an active process of immune‐regulation in which activated T cells undergo apoptosis. We studied Fas ligand (FasL) expression and apoptosis in normal and pathologic placentas to find out whether the Fas‐FasL‐induced apoptosis takes place during implantation. METHOD OF STUDY: FasL expression in paraffin sections was detected using specific antibodies and confirmed with reverse transcriptase‐polymerase chain reaction of total RNA from frozen placentas. Apoptosis was detected using the terminal deoxy (d)‐UTP nick end‐labeling assay. RESULTS: FasL was found in the normal placenta and in gestational trophoblastic disease. Apoptotic leukocytes were localized to the maternal‐fetal interface corresponding in localization with the distribution of FasL. CONCLUSIONS: We propose that FasL expression in the placenta is a mechanism responsible for the development of maternal immune tolerance specific for paternal alloantigens and operates in pathologic states characterized by trophoblastic invasion/proliferation.