The killer cell inhibitory receptors (KIR) of human natural killer (NK) cells recognize human leukocyte antigen class I molecules and inhibit NK cell cytotoxicity through their interaction with protein tyrosine phosphatases (PTP). Here, we report that KIR recognition of class I ligands inhibits distal signaling events and ultimately NK cell cytotoxicity by blocking the association of an adaptor...

NK cells that populate the decidua are important regulators of normal placentation. In contrast to peripheral blood NK cells, decidual NK (dNK) cells lack cytotoxicity, secrete proangiogenic factors, and regulate trophoblast invasion. In this study we show that exposure to a combination of hypoxia, TGF-β1, and a demethylating agent results in NK cells that express killer cell Ig-like receptors,...

Natural killer (NK) cells are essential for killing transformed and virally infected cells. To prevent auto-reactivity, NK cell activation is inhibited by inhibitory receptors that activate the tyrosine phosphatase SHP-1, which dephosphorylates signaling molecules crucial for NK cell activation. Initially, only a single SHP-1 substrate was identified in NK cells, the GEF VAV1. We recently demon...

NK cell cytotoxicity requires two positive signals for killing of tumors. Activation receptors induce polarization of the microtubule organization center and degranulation, while leukocyte function-associated antigen (LFA)-1 is required for conjugate formation and actin polymerization and under some circumstances may be sufficient for NK cell cytotoxicity. Although the receptor for direct killi...

A t early times during viral infections, natural killer (NK) cells can contribute to direct antiviral defense (1, 2). The effect is most dramatic when they are stimulated to release the contents of their cytolytic granules for lysis of virus-infected target cells. Type 1 interferons (IFNs), produced during innate responses to infections, induce elevated NK cell cytotoxicity. Killing, however, i...

The redox-active chlorite-based drug WF10 (Immunokine) was shown to have modulatory effects on both the innate and adaptive immune system in vitro and in vivo. Animal studies suggest that WF10 enhances immunity against tumors. One possible explanation for such an effect is that WF10 stimulates natural killer cell cytotoxicity against malignant cells. Here, we show that WF10 regulates human NK c...

Natural killer (NK) cells serve as one of the first lines of defense against viral infections and transformed cells. NK cell cytotoxicity is not dependent on antigen presentation by target cells, but is dependent on integration of activating and inhibitory signals triggered by receptor-ligand interactions formed at a tight intercellular contact between the NK and target cell, i.e., the immune s...

We tested the effect of three different interferon-(IFN) inducing pyrimidinone molecules with cancer therapeutic potential on natural killer (NK) cells. Peritoneal exudate (PE) cells were selected for these studies because their NK cell cytotoxicity is very low. Augmentation of PE-NK cell cytotoxicity was observed in eight different strains of mice after i.p. administration of 250 mg/kg of each...

BACKGROUND AND AIM NK cells are one of the major immune cells in endometriosis pathogenesis. While previous clinical studies have shown that helixor A to be an effective treatment for endometriosis, little is known about its mechanism of action, or its relationship with immune cells. The aim of this study is to investigate the effects of helixor A on Natural killer cell (NK cell) cytotoxicity i...