Unique Receptor Repertoire in Mouse Uterine NK cells

Abstract

Uterine NK (uNK) cells are a prominent feature of the uterine mucosa and regulate placentation. NK cell activity is regulated by a balance of activating and inhibitory receptors, however the receptor repertoire of mouse uNK cells is unknown. We describe herein two distinct subsets of CD3−CD122+ NK cells in the mouse uterus (comprising decidua and mesometrial lymphoid aggregate of pregnancy) at mid-gestation: a small subset indistinguishable from peripheral NK cells, and a larger subset that expresses NKp46 and Ly49 receptors, but not NK1.1 or DX5. This larger subset reacts with Dolichus biflores agglutinin, a marker of uNK cells in the mouse, and is adjacent to the invading trophoblast. By multiparametric analysis we show that the phenotype of uNK cells is unique and unprecedented in terms of adhesion, activation, and MHC binding potential. Thus, the Ly49 repertoire and the expression of other differentiation markers strikingly distinguish uNK cells from peripheral NK cells, suggesting that a selection process shapes the receptor repertoire of mouse uNK cells.

Paternal MHC expression on mouse trophoblast affects uterine vascularization and fetal growth

“…The cell surface localization of H2-K would allow for a functional interaction with maternal immune cells, in particular with the cognate Ly49 receptors on the surface of uNK cells (15). Indeed, we found that paternal H2-K b affected the maternal uNK cell repertoire, because more Ly49C-positive uNK cells were detected in the decidua of (d × b) allogeneic crosses compared with (d × d) syngeneic controls (Fig.…”

“…Indeed, uterine NK (uNK) cells are the most likely maternal cell type to interact with trophoblast antigens in the decidua basalis because of their sheer abundance: they constitute 70% of all maternal leukocytes in the placental bed (14). uNK cells differ from peripheral NK cells in that they have a reduced lytic activity and a distinct surface receptor repertoire (14)(15)(16)(17). uNK cells support neovascularization of the decidua by producing proangiogenic and endothelial mitogenic stimulants and contribute to arterial transformation by initiating the loss of the arterial media (5,14,18,19).…”

Reduced Stathmin-1 Expression in Natural Killer Cells Associated with Spontaneous Abortion

“…A cell purification strategy using DBA-lectin and CD122 marker may be more specific for mouse uNK cell purification. 22 However, microbead-conjugated antibodies for DBA-lectin or CD122 are not commercially available. At present, microbead-conjugated anti-CD49b is used in MACS to purify uNK cells.…”

“…27 A recent report suggested that CD122 is a good marker for uNK cells. 22 To define the percentage of CD122 ϩ cells in the CD49b ϩ population, we performed two-color flow cytometry using MACS-purified CD49b ϩ cells stained with FITC-conjugated anti-CD122 and PE-conjugated antiCD49b antibodies, which showed that most CD49b ϩ cells were also positive for CD122 in CBA/JϫDBA/2J and CBA/JϫBALB/c mice.…”

“…As indicated in Figure 5 The murine cells positive for DBA-lectin were scattered intensively in decidual basalis tissue and in the mesometrial lymphoid aggregate of pregnancy in both matings, whereas no DBA-lectin ϩ cells were observed in placenta tissue (region P) ( Figure 5, E and F). 22 The mean density of stathmin-1 ϩ DBA-lectin ϩ cells was determined using Image-Pro Plus 6.0 (Media Cybernetics Inc., Bethesda, MD). The mean Ϯ SD density of the doublepositive cells was significantly higher in CBA/JϫBALB/c matings than in CBA/JϫDBA/2J matings (9.6 Ϯ 5.5 versus 1.0 Ϯ 0.9; P Ͻ 0.01) ( Figure 5G).…”