Contributions from Self-Renewal and Trafficking to the Uterine NK Cell Population of Early Pregnancy

Abstract

Uterine NK (uNK) cells are abundant in human and murine uteri during decidualization. It is unclear whether precursors of uNK (pre-uNK) cells self-renew or are recruited from other sites. To assess self-renewal of pre-uNK cells, uterine segments from NK cell-competent mice were grafted orthotopically into NK/uNK cell-deficient or wild-type mice. Only in wild-type recipients did decidualized grafts contain uNK cells, indicating that pre-uNK cells do not self-renew in uterus. To identify pre-uNK cell sources, thymus, bone marrow, lymph node, or spleen cells were grafted from virgin or pregnant NK cell-competent donors into mated NK/uNK cell-deficient recipients. Cells from secondary lymphoid tissues of pregnant donors gave high level uNK cell reconstitution, which was independent of chemokine receptors CCR2 or CCR5. Pregnancy-induced changes to lymphocyte-endothelial cell interactions were documented using adhesion of human lymphocytes to frozen mouse tissue sections under shear. A dynamic increase was observed in L-selectin- and α4 integrin-dependent adhesion of CD56bright NK cells to decidualizing uterus and in human PBL adhesion to lymph node endothelium. These data support a model that attributes the dramatic increases in human and murine uNK cells during decidualization to precursor cell recruitment.

TGFβ promotes conversion of CD16+peripheral blood NK cells into CD16−NK cells with similarities to decidual NK cells

“…Subsets of Lin Ϫ CD34 ϩ cells isolated from decidua also appear to express other markers associated with NK progenitor cells including integrin ␤7, and CD117 (data not shown). However, in mice, elegant cell transfer studies into NK cell-deficient animals suggested that dNK cell precursors were not present in uterine grafts, but could be found in secondary lymphoid tissues (41,42).…”

Aberrant Endometrial Features of Pregnancy in Diabetic NOD Mice

“…This donor had normal random and fasting blood glucose, insulin, and lipid profiles. Peripheral blood lymphocytes were isolated as previously described (24,29), adjusted to 5 ϫ 10 6 cells/l in serum-free RPMI and incubated with anti-CD56 mAb (1:100; Coulter Immunology, Hialeah, FL).…”

“…These changes are completed histologically in mice by midpregnancy (gestation day [gd] 10 of a 19-to 20-day term [23]). Transplantable uNK progenitor cells are not found in mouse uteri but occur in all peripheral lymphoid tissues (24). Although hematopoeitic stem cells occur in human uteri (25), in vitro assays show that human CD56 bright blood NK cells, the minor blood NK cell type, gain in functional interactions with endothelium of the decidua basalis at the preovulatory menstrual cycle surge in luteinizing hormone.…”

Natural killer cell-triggered vascular transformation: maternal care before birth?

“…Neither decidualized grafts nor decidualized host uterus differentiated uNK cells, strongly suggesting that most uNK cell progenitors are recruited from the circulation. 13 In that study and most studies reported prior to 1995, mouse uNK cells were recognized by their lymphoid shape and the reactivity of their cytoplasmic granules with periodic acid Schiff's (PAS) reagent, a histochemical stain for glycoproteins, especially mucin. 14 Over the past decade, most investigators of mouse uNK cells have switched to use of the lectin Dolichos biflorus agglutinin (DBA) which reacts with terminal N-acetyl-D-galactosamine, for uNK cell identification.…”