Natural killer cells and reproduction

Moffett-King, Ashley; Entrican, Gary; Ellis, Shirley A.; Hutchinson, James A.; Bainbridge, D. R. J.

doi:10.1016/s1471-4906(02)02261-5

Cited by 46 publications

(29 citation statements)

References 5 publications

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“…Furthermore, we found that 100% of dNK cells expressing NKp46 also express NKG2A (data not shown). Such negative control of NKp46 cytolytic potential is likely to occur in normal healthy pregnancy as the HLA-E specific ligand of CD94/ NKG2A is expressed by the invading extravillous trophoblast, the only "nonself" target cells present in the decidua basalis and in direct contact with dNK (32)(33)(34) The second explanation could be that in normal pregnancy there is no NKp46 ligand expressed on local maternal uterine cells, as recently demonstrated (35). It has been shown that fresh dNK exert reduced lytic activity on K562 or 721.221 target cells, unless they were incubated with IL-15 (15).…”

Section: Discussionmentioning

confidence: 99%

Critical and Differential Roles of NKp46- and NKp30-Activating Receptors Expressed by Uterine NK Cells in Early Pregnancy

Costa

Casemayou

Aguerre-Girr

et al. 2008

The Journal of Immunology

128

150

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In early human pregnancy, uterine decidual NK cells (dNK) are abundant and considered as cytokine producers but poorly cytotoxic despite their cytolytic granule content, suggesting a negative control of this latter effector function. To investigate the basis of this control, we examined the relative contribution to the cytotoxic function of different activating receptors expressed by dNK. Using a multicolor flow cytometry analysis, we found that freshly isolated dNK exhibit a unique repertoire of activating and inhibitory receptors, identical among all the donors tested. We then demonstrated that in fresh dNK, mAb-specific engagement of NKp46-, and to a lesser extent NKG2C-, but not NKp30-activating receptors induced intracellular calcium mobilization, perforin polarization, granule exocytosis and efficient target cell lysis. NKp46-mediated cytotoxicity is coactivated by CD2 but dramatically blocked by NKG2A coengagement, indicating that the dNK cytotoxic potential could be tightly controlled in vivo. We finally found that in dNK, mAb-specific engagement of NKp30, but not NKp46, triggered the production of IFN-γ, TNF-α, MIP-1α, MIP-1β, and GM-CSF proinflammatory molecules. These data demonstrate a differential, controlled role of NKp46- and NKp30-activating receptors expressed by dNK that could be critical for the outcome of pregnancy and the killing of uterine cells infected by pathogens.

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Section: Discussionmentioning

confidence: 99%

Critical and Differential Roles of NKp46- and NKp30-Activating Receptors Expressed by Uterine NK Cells in Early Pregnancy

Costa

Casemayou

Aguerre-Girr

et al. 2008

The Journal of Immunology

128

150

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“…21,22 They play an important role in controlling trophoblast invasion and express receptors that interact with ligands expressed on trophoblast. 23 NK cells are an important regulator of spiral artery remodeling and maintenance of decidual integrity. 24 Fu et al demonstrated that NK cells regulate pathogenic T helper 17 (Th17) cells at the maternal-fetal interface and thus promote immune tolerance and maintenance of pregnancy.…”

Section: Nk Cells During Various Phases Of Human Lifementioning

confidence: 99%

Natural killer cells

Mandal¹,

Viswanathan²

2015

Hematology/Oncology and Stem Cell Therapy

240

179

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Natural killer (NK) cells constitute our bodies' frontline defense system, guarding against tumors and launching attacks against infections. The activities of NK cells are regulated by the interaction of various receptors expressed on their surfaces with cell surface ligands. While the role of NK cells in controlling tumor activity is relatively clear, the fact that they are also linked to various other disease conditions is now being highlighted. Here, we present an overview of the role of NK cells during normal body state as well as under diseased state. We discuss the possible utilization of these powerful cells as immunotherapeutic agents in combating diseases such as asthma, autoimmune diseases, and HIV-AIDS. This review also outlines current challenges in NK cell therapy.

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“…Furthermore, the early pregnant uterus of different mammalian species homes numerous maternal lymphocytes, predominantly a specific subset of NK cells, that could reject the embryo unless they are tolerized by yet to be understood mechanisms [1][2][3][4]. In humans, maternal immune tolerance to the conceptus could be related to the unusual expression profile of MHC class I molecules in the placental extravillous cytotrophoblast.…”

Section: Introductionmentioning

confidence: 99%

Recognition of HLA‐G by the NK cell receptor KIR2DL4 is not essential for human reproduction

et al. 2003

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A central issue of reproductive immunology in mammals is why a semi-allogeneic embryo is not rejected by the pregnant mother. This is particularly intriguing since, in different species, the early pregnant uterus is infiltrated by numerous maternal lymphocytes, predominantly NK cells. The human NK cell receptor KIR2DL4 has been implicated in the maternal tolerance to the embryo due to its recognition of HLA-G, a non-classical MHC molecule expressed preferentially in the placenta. Killer cell Ig-like receptors (KIR) are believed to participate in the natural immunity to infection and tumors, but KIR2DL4 has unique structural, functional and genetic features that could confer it a different role. However, we demonstrate here that the KIR2DL4:HLA-G interaction is not essential for human reproduction by showing that a multiparous woman lacks a KIR2DL4 gene.

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Natural killer cells and reproduction

Cited by 46 publications

References 5 publications

Critical and Differential Roles of NKp46- and NKp30-Activating Receptors Expressed by Uterine NK Cells in Early Pregnancy

Critical and Differential Roles of NKp46- and NKp30-Activating Receptors Expressed by Uterine NK Cells in Early Pregnancy

Natural killer cells

Recognition of HLA‐G by the NK cell receptor KIR2DL4 is not essential for human reproduction

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