A Murine Model of NK Cell Mediated Resorption

Abstract

There is increasing evidence that some models of immunologically mediated murine embryo demise involve nonspecific lytic effector cells. In this paper, we use two double stranded synthetic RNAs, known as potent interferon inducers and NK cell activators, the Poly (I). Poly (C) and the less toxic Poly (I). Poly (C12U). These polynucleotides enhance fetal resorption rates in both resorption prone and none-resorption prone strains of mice. We have studied the kinetics of the phenomenon, and observed an anti-implantation-like effect of early injection during early pregnancy. The abortifacient effects can be adoptively transferred to naive recipients by spleen cells from Ds RNA injected donors. Such effects are abrogated if the cells are pretreated with anti-NK cell antiserum. The relevance of these findings to the survival of the conceptus is suggested.

Pregnancy specific glycoprotein 18 induces IL-10 expression in murine macrophages

“…On the other hand, IL-10 induces HLA-G expression, which inhibits lysis by maternal NK cells in trophoblasts and monocytes [42]. Interestingly, induction of NK and LAK cell activity has been linked to spontaneous fetal resorption in mice [43]. In addition, IL-10 has been shown to inhibit human placental cytotrophoblast invasiveness and metalloproteinase production in human mononuclear phagocytes and a deficiency in placental IL-10 was associated with pre-eclampsia [44][45][46].…”

The Water Channel Aquaporin 1 Is a Novel Molecular Target of Polychlorinated Biphenyls for in Utero Anomalies

“…IL-10 is produced by gestational tissue and maternal immune cells in the intrauterine microenvironment in humans (8,9) and in mice (10). We and others have reported that IL-10 Ϫ/Ϫ mice experience preterm birth and resorptions in response to low doses of inflammatory triggers such as lipopolysaccharide (LPS) (11,12) or poly(I-C) (13). Importantly, the pregnancy outcome in treated IL-10 Ϫ/Ϫ mice can be rescued by giving an exogenous dose of IL-10 (11,14).…”

Vascular Endothelial Growth Factor C Facilitates Immune Tolerance and Endovascular Activity of Human Uterine NK Cells at the Maternal-Fetal Interface

“…This suggests that these innate cells retain their primordial role as sentinels with an ability to attack target cells in response to “danger signals” in their proximate milieu. Indeed, recent studies from our laboratory and others have shown that uNK cells “switch on” their cytolytic machinery leading to fetal resorption or preterm birth in mice exposed to lipopolysaccharide (LPS) (25, 26) or dsRNA (27). In addition, increased cytolytic CD16 + NK cells have been reported in the endometrium of patients with a history of recurrent spontaneous abortion and implantation failure (28–30).…”