Fas-fas ligand system-induced apoptosis in human placenta and gestational trophoblastic disease.
OBJECTIVE
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.


METHODS
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.
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, CT 06520-8063, USA.
G
G
Mor
L S
LS
Gutierrez
M
M
Eliza
F
F
Kahyaoglu
A
A
Arici
D017209:Apoptosis; D002822:Choriocarcinoma / Q000276:immunology; D053222:Fas Ligand Protein; D005260:Female; D005333:Fetus / Q000276:immunology; D006801:Humans; D006828:Hydatidiform Mole / Q000276:immunology; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D010920:Placenta / Q000276:immunology*; D016133:Polymerase Chain Reaction; D011247:Pregnancy / Q000276:immunology*; D011261:Pregnancy Trimester, First / Q000276:immunology; D011263:Pregnancy Trimester, Third / Q000276:immunology; D014327:Trophoblasts / Q000276:immunology; D014594:Uterine Neoplasms / Q000276:immunology; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor