Fas-ligand expression by human trophoblasts: Implications for fetal survival and immune privilege

The human placental micro-environment functions as an immuneprivileged site which protects the fetus from maternal immune responses. Correlating with other immune privileged sites, it is tempting to speculate that programmed cell death (apoptosis) may play an important role in the ability of trophoblasts to restrict the trafficking of maternal immune cells in the placenta. Protection from CD95 (Fas)-mediated apoptosis has been shown to be an important event in the other immuneprivileged organ sites such as the cornea, the testis as well as in malignancies such as melanoma and colon carcinoma. This immunoprotection is thought to be mediated by Fas and Fas-ligand (Fas-L) interactions. The interaction of Fas with Fas-L regulates a number of physiological and pathological processes of cell death. We hypothesize that trophoblasts derived from human placenta express functional Fas-L which confers immuneprivileged status to the fetus. Placental tissues obtained from different gestational ages were stained for Fas-ligand expression by immunohistochemistry. Normal IgG was used as a control. Cytotrophoblasts and syncytiotrophoblasts from early and late stages of gestation showed Fas-ligand expression. Next, cytotrophoblasts were isolated from early and late gestational ages using trypsin-DNase digestion followed by separation on a discontinuous percoll gradient. The cells were then treated with mitomycin-C to inhibit DNA synthesis. The cytotrophoblasts were co-cultured with Fas expressing Jurkat cells and the growth arrest in Jurkat cells was assessed by ³H- thymidine uptake. Colon carcinoma cell line (SW-620) was used as positive controls for Fas-L expression. Cytotrophoblasts from both early and late gestational ages inhibited growth in the Jurkat cells. Similar results were obtained in the control SW-620 cell line. We conclude that trophoblasts express functional Fas-ligand and this may play an important role in conferring the immuneprivileged status to the fetus.