Labor-associated changes in Fas ligand expression and function in human placenta

Fas ligand (FasL)-dependent apoptosis has been implicated in the control of tissue-damaging inflammatory responses in several immune privileged sites. Here, we present data demonstrating that FasL is expressed on human tropho blast cells throughout pregnancy and transduces growth inhibitory/death sig nals in cells bearing its receptor, Fas (CD95). Immunohistochemical analysi s detected FasL-positive staining in the trophoblast layer of villi of firs t- and second-trimester and term (no labor) placental tissues, as well as i n freshly isolated cytotrophoblasts representing these gestational ages. In contrast, term placental tissues and cytotrophoblasts from labor-associate d deliveries exhibited significantly reduced FasL expression, suggesting th at parturition altered the characteristics of trophoblast cells. FasL-speci fic immunoblotting of cytotrophoblast cell lysates further confirmed these results. To assess the functionality of FasL expressed on cytotrophoblasts, we co-cultured these cells with Fas-bearing Jurkat T cells. Cytotrophoblas ts from early pregnancy, or term with no labor, significantly inhibited gro wth in Jurkat cells, evident even at a 1:1 effector:target cell ratio, as d etermined by the incorporation of [H-3]thymidine. Similar results were obta ined when a FasL-positive colon carcinoma cell line, SW620, was used in pla ce of cytotrophoblasts. Tn contrast, term cytotrophoblasts from labor deliv eries exhibited poor FasL expression and were quantitatively much less prof icient in inhibiting [H-3]thymidine incorporation in Jurkat cells. These da ta indicate that FasL could participate in modulating the inflammatory resp onses associated with labor and suggest intrinsic molecular differences in the placental microenvironment before and after labor.