Apoptotic DC-SIGN+ cells in normal human decidua

Abstract

Background: Normal pregnancy and spontaneous abortion in humans and mice are associated with immune responses. The decidua harbors dendritic cells identifiable in humans by their expression of DC-SIGN. Because dendritic cells are essential for immune response regulation, decidual DC-SIGN+ cells may play a role in normal or pathological pregnancy outcomes. Previous reports suggested that DC interact with NK cells in decidua, although the functional significance of this phenomenon remains unknown. Objective: We studied the presence of conjugates of DC-SIGN+ cells with CD56+ NK cells in normal human decidua. Methods: Conjugates of DC-SIGN+ cells with CD56+ NK cells were studied in leukocyte suspensions of normal human decidua (6-11 weeks) by flow cytometry and confocal microscopy. The presence of apoptotic cells was determined by the TUNEL assay, incubation with annexin V and confocal microscopy in decidual leukocyte suspensions and by the TUNEL assay in decidual sections. Results: We observed conjugates of decidual DC-SIGN+ cells with CD56+ NK cells (40.2 ± 26.1% of all the DC-SIGN+ cells by flow cytometry and 52.3 ± 10.2% by confocal microscopy). We also found that a proportion of DC-SIGN+ cells were in apoptosis, since they were TUNEL+ (40.2 ± 7.2% of all DC-SIGN+ cells in decidual sections) and annexin V+ (34.4 ± 15.2% in leukocyte suspensions). And sorted DC-SIGN+ cells had multilobulated nuclei. Conclusions: The conjugates of decidual DC-SIGN+ cells with CD56+ NK cells strongly suggest that these latter cells induce apoptosis in DC-SIGN+ cells during normal pregnancy. We discuss this possibility in the context of maternal-fetal tolerance.