Accumulation of CD16⁻CD56⁺ natural killer cells with high affinity interleukin 2 receptors in human early pregnancy decidua

Abstract

Most human peripheral blood natural killer (NK) cells express the phenotype CD16+CD56+. However, a very minor subset of NK cells express CD16-CD56+, and these NK cells bear both interleukin 2 receptor (IL-2R)alpha (p55) and IL-2R beta (p75) (high affinity IL-2 receptors). In this report, we demonstrate that in human early pregnancy decidua--an interface between maternal immunocompetent cells and fetus (placenta)--abundant (approximately 83%) CD16-CD56+ NK cells with high affinity IL-2 receptors were present, and these cells responded to low amounts of IL-2 (4.5 pM). These CD16-CD56+ NK cells significantly expressed an early activation antigen, CD69, in vivo, whereas peripheral CD16-CD56+ NK cells did not express CD69. These findings suggest that CD16-CD56+ NK cells in early pregnancy decidua may be activated in vivo, and may play an important role in immunoregulation during early pregnancy. Also, decidual lymphocytes may be useful materials to study the mechanism of MHC-unrestricted cytotoxicity of this type of NK cells.

Embryonic Resorption and Polycyclic Aromatic Hydrocarbons: Putative Immune-mediated Mechanisms

“…À NK cells represent the vast majority of immune cells in the early pregnancy decidua [Moffett-King 2002;Nishikawa et al 1991]. A recent study showed that accumulation of CD56 bright , granulysin-positive uNK cells in the decidua basalis was linked to pregnancy loss in humans [Nakashima et al 2008].…”

Interleukin 15: biology and relevance to human disease

“…140 Similar NK-like cells have also been identified in the human uterus and have the phenotype CD56 bright CD16 Ϫ . 141,142 These NK cells are located at the maternal/ fetal junction and are thought to play a role in regulating implantation and trophoblast invasion, but the factors governing their localization or differentiation are unclear. 143 Uterine NK cells express IL-15R components, and IL-15 increases the expression of NK cytolytic mediators (perforin and granzymes) in pregnant uterine tissue explanted in vitro, 144 as well as in primary mouse uterine NK cells.…”

Granulysin Produced by Uterine Natural Killer Cells Induces Apoptosis of Extravillous Trophoblasts in Spontaneous Abortion

“…4,5 NK cells interact with target cells by a series of inhibitory and activating NK cell receptors constitutively expressed by uNK cells. Furthermore, CD16…”

“…The decidual mononuclear cells (leukocytes) were purified by the standard Ficoll-Hypaque (Nycomed Pharma, Oslo, Norway) density gradient centrifugation after homogenization and filtration through a 32-mm nylon mesh as previously reported. 4 The cells were then suspended in RPMI 1640 medium supplemented with 10% fetal calf serum, 100 U/ml penicillin, and 100 g/ml streptomycin, and incubated for 2 hours at 37°C in an atmosphere of 5% CO 2 to allow adherent cells to attach to the plastic. The supernatant containing decidual lymphocytes was then collected and the cells were used for analysis.…”