NK Cells Detect Changes in Adaptive Immunity within Mouse Decidua from Gestation Day Eight

Abstract

Viable human CD56+CD16− peripheral blood Natural Killer (NK) cells show specific in vitro binding under shear forces to ligands expressed by endothelial cells in cryostat sections of gestation day (gd)7 mouse decidua basalis. In serial assays, numbers of cells adhering to gd7 tissue are constant for men but have cyclical variation for fertile women, suggesting a brief gain in functional decidual homing potential of this NK cell subset during the menstrual cycle. Regardless of gender, numbers of adhering cells from an individual donor, increase dramatically when the substrate is decidua basalis from a later gestational timepoint. Here, we report that human blood CD56+CD16− NK cells which adhere as single cells over gd7 decidua basalis, adhere as large clusters over gd8 and gd9 tissues, suggestive of antigen recognition and lymphocyte activation. We asked which cells within mouse decidua basalis trigger this response in CD56+CD16− cells. Using decidua from mice transgenic for myeloid dendritic cell (mDC) expression of enhanced yellow fluorescent protein (eYFP), we found cluster formation was independent of mDC contact. Use of decidua from alymphoid mice showed clustering behavior required substrate lymphocytes. By use of decidua containing NK cells but lacking T and B cells, decidual T and/or B lymphocytes were identified as the cells altered after gd7 in a manner that activates CD56+CD16− cell clustering. This time point is just prior to mouse spiral arterial modification and its detection by these indicator cells implicates adaptive, decidual immune responses in the regulation of NK cell function.

Imaging of Vascular Development in Early Mouse Decidua and Its Association with Leukocytes and Trophoblasts1

“…Although NK cells and T cells expressed activation markers from GD 4.5, morphologic evidence for activation (leukocyte conjugate formation and for migration suggested by shape changes) was uncommon before GD 8.5, which is 4-5 days after blastocyst hatching and, thus, a time consistent with primary immune responses to antigens exposed at hatching. It is also the GD at which human indicator blood lymphocytes used in assays of adhesion to mouse decidual substrates first recognize changes in mouse decidual T cells and conjugate with them [34]. The most highly activated cells (CD69 þ ) in early decidua appear to be uNK cells, as reported in older lytic function assays [35].…”

Altered DNA Methylation in Leukocytes with Trisomy 21

“…NK cells were purified from human blood to >90% purity using immunomagnetic beads as previously described [54] . T-cells were isolated from blood of adults with DS and normal adult controls to >80% purity using a RosetteSep Kit (Sigma) according to the manufacturer's instructions.…”

Circulating CD56+ cells of diabetic women show deviated homing potential for specific tissues during and following pregnancy

“…The defined lymphocyte-endothelial cell interactions were localized to decidua basalis and they increased in frequency as decidua matured (i.e. when simultaneous assays of adhesion were conducted on sections of gestation day (gd)6 to gd10 deciduas) (Chantakru et al, 2003a;Hatta et al, 2009). L-selectin (SELL) and alpha 4 integrin (ITGA) were identified in blocking studies as the molecules supporting the functional, shear-force resistant interactions between viable blood NK cells and decidual endothelium.…”