Human Decidual Natural Killer Cells Are a Unique NK Cell Subset with Immunomodulatory Potential

Abstract

Natural killer cells constitute 50–90% of lymphocytes in human uterine decidua in early pregnancy. Here, CD56bright uterine decidual NK (dNK) cells were compared with the CD56bright and CD56dim peripheral NK cell subsets by microarray analysis, with verification of results by flow cytometry and RT-PCR. Among the ∼10,000 genes studied, 278 genes showed at least a threefold change with P ≤ 0.001 when comparing the dNK and peripheral NK cell subsets, most displaying increased expression in dNK cells. The largest number of these encoded surface proteins, including the unusual lectinlike receptors NKG2E and Ly-49L, several killer cell Ig-like receptors, the integrin subunits αD, αX, β1, and β5, and multiple tetraspanins (CD9, CD151, CD53, CD63, and TSPAN-5). Additionally, two secreted proteins, galectin-1 and progestagen-associated protein 14, known to have immunomodulatory functions, were selectively expressed in dNK cells.

NK Cells Inhibit T Cell Proliferation via p21-Mediated Cell Cycle Arrest

“…The bone marrow NK cell subset may have an immunomodulatory capacity that spleen NK cells may lack and vice versa. For example, human decidual, but not peripheral, NK cells can express proteins that have immunomodulatory function and are postulated to play an important role in maternal-fetal tolerance (8). We are currently performing experiments to characterize the bone marrow NK cell subset more thoroughly and compare it to the splenic NK cells to determine the phenotypic and functional differences in these subsets.…”

“…Activated human NK cells were shown to influence the function of autologous DCs via direct cell-cell interaction, suggesting that they may have a role in regulating Ag presentation and T cell priming (2-7). NK cells have been shown to play an immunomodulatory role in maternal-fetal tolerance (8) and to regulate proliferation and Ab production by B cells (9).…”

17β-Estradiol Suppresses Cytotoxicity and Proliferative Capacity of Murine Splenic NK1.1+ Cells

“…The filtrate containing single cells was spun down at 1,500 rpm for 5 min. The obtained single splenic cells were treated with ACK lysing buffer (0.15 M NH 4 Cl, 1.0 mM KHCO 3 , 0.1 mM EDTA, pH 7.2) for 5 min to lyse the erythrocytes, and then washed thrice with RPMI 1640 medium containing 10% FCS. NK cells were enriched by magnetic positive selection using anti-DX5 microbeads following the manufacturer's protocol.…”

“…The dominant lymphocytes in human and murine implantation sites are transient, pregnancy-associated uterine natural killer (uNK) cells, which account for about 70% of resident lymphocytes in human decidual cell suspensions (3). Thus, uNK cells may play a role in implantation and pregnancy, at least in early gestation (4). Otherwise, uNK cells may derive predominantly from a subset of peripheral NK cells, which were recruited to the decidua of the uterus of pregnant woman under hormonal influence (5).…”

Immune response in silico (IRIS): immune-specific genes identified from a compendium of microarray expression data

“…Microarray experiments have been carried out on various immune cell subsets by a number of different investigators in order to understand gene expression differences during differentiation and activation. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] These studies have provided invaluable insight into comprehensive gene expression profiles that define many different immune cell subsets and states of differentiation and activation. In particular, a recent study detailed elegantly the genes expressed specifically in many subsets of the T-cell lineage.…”