Apoptotic DC-SIGN+ cells in normal human decidua

Abstract

BackgroundNormal 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. ObjectiveWe studied the presence of conjugates of DC-SIGN+ cells with CD56+ NK cells in normal human decidua. MethodsConjugates 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. ResultsWe 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. ConclusionsThe 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.