TRAIL (Apo-2L) and TRAIL receptors in human placentas: Implications for immune privilege

Mechanisms accounting for protection of the fetal semiallograft from matern al immune cells remain incompletely understood, In other contexts, interact ions between TRAIL (TNF-related apoptosis-inducing ligand/Apo-2L) and its r eceptors kill activated lymphocytes, The purpose of this study was therefor e to investigate the potential of the TRAIL/TRAIL-R system to protect the p lacenta against immune cell attack. Analysis by Northern blotting demonstra ted mRNAs encoding TRAIL as well as the four TRAIL receptors (DR4, DR5, DcR I/TRID, DcR2/TRUNDD) in human placentas. Immunohistochemical experiments de monstrated that TRAIL protein is prominent in syncytiotrophoblast, an unint errupted placental cell layer that is continuously exposed to maternal bloo d, as well as in macrophage-like placental mesenchymal cells (Hofbauer cell s). Studies on cell lines representing trophoblasts (Jar, JEG3 cells) and m acrophages (U937, THP-1 cells) showed that both lineages contained TRAIL mR NA and that steady state levels of transcripts were increased 2- to 11-fold by IFN-gamma, By contrast, cell lineage-specific differences were observed in expression of the TRAIL-R genes. Although all four lines contained mRNA encoding the apoptosis-inducing DR5 receptor, only trophoblast cells conta ined mRNA encoding the DcR1 decoy receptor and only macrophages contained D cR2 decoy receptor transcripts. DR4 mRNA was present only in THP-1 cells an d was the only TRAIL-R transcript increased by IFN-gamma, Cytotoxicity assa ys revealed that the two trophoblast cell lines were resistant, whereas the two macrophage lines were partially susceptible to killing by rTRAIL, Coll ectively, the results are consistent with a role for the TRAIL/TRAIL-R syst em in the establishment of placental immune privilege.