scholarly journals NK Cells and Trophoblasts

2004 ◽  
Vol 200 (8) ◽  
pp. 951-955 ◽  
Author(s):  
Peter Parham

In placental mammals, viviparity—the production of living young within the mother's body—evolved under the auspices of the immune system. Elements of immunity were incorporated, giving pregnancy a mildly inflammatory character. Formation of the placenta, the organ that feeds the fetus, involves a cooperation between maternal natural killer (NK) cells and fetal trophoblast cells that remodels the blood supply. Recent research reveals that this process and human reproductive success are influenced by polymorphic HLA-C ligands and their killer cell immunoglobulin-like receptors (KIR).

Endocrines ◽  
2021 ◽  
Vol 2 (2) ◽  
pp. 121-132
Author(s):  
Erik D. Hanson ◽  
Lauren C. Bates ◽  
Kaileigh Moertl ◽  
Elizabeth S. Evans

Natural killer (NK) cells from the innate immune system are integral to overall immunity and also in managing the tumor burden during cancer. Breast (BCa) and prostate cancer (PCa) are the most common tumors in U.S. adults. Both BCa and PCa are frequently treated with hormone suppression therapies that are associated with numerous adverse effects including direct effects on the immune system. Regular exercise is recommended for cancer survivors to reduce side effects and improve quality of life. Acute exercise is a potent stimulus for NK cells in healthy individuals with current evidence indicating that NK mobilization in individuals with BCa and PCa is comparable. NK cell mobilization results from elevations in shear stress and catecholamine levels. Despite a normal NK cell response to exercise, increases in epinephrine are attenuated in BCa and PCa. The significance of this potential discrepancy still needs to be determined. However, alterations in adrenal hormone signaling are hypothesized to be due to chronic stress during cancer treatment. Additional compensatory factors induced by exercise are reviewed along with recommendations on standardized approaches to be used in exercise immunology studies involving oncology populations.


1999 ◽  
Vol 189 (7) ◽  
pp. 1093-1100 ◽  
Author(s):  
Sumati Rajagopalan ◽  
Eric O. Long

Human natural killer (NK) cells express several killer cell immunoglobulin (Ig)-like receptors (KIRs) that inhibit their cytotoxicity upon recognition of human histocompatibility leukocyte antigen (HLA) class I molecules on target cells. Additional members of the KIR family, including some that deliver activation signals, have unknown ligand specificity and function. One such KIR, denoted KIR2DL4, is structurally divergent from other KIRs in the configuration of its two extracellular Ig domains and of its transmembrane and cytoplasmic domains. Here we show that recombinant soluble KIR2DL4 binds to cells expressing HLA-G but not to cells expressing other HLA class I molecules. Unlike other HLA class I–specific KIRs, which are clonally distributed on NK cells, KIR2DL4 is expressed at the surface of all NK cells. Furthermore, functional transfer of KIR2DL4 into the cell line NK-92 resulted in inhibition of lysis of target cells that express HLA-G, but not target cells that express other class I molecules including HLA-E. Therefore, given that HLA-G expression is restricted to fetal trophoblast cells, KIR2DL4 may provide important signals to maternal NK decidual cells that interact with trophoblast cells at the maternal–fetal interface during pregnancy.


2020 ◽  
Vol 38 (1) ◽  
pp. 511-539
Author(s):  
Mathieu Mancini ◽  
Silvia M. Vidal

The continuous interactions between host and pathogens during their coevolution have shaped both the immune system and the countermeasures used by pathogens. Natural killer (NK) cells are innate lymphocytes that are considered central players in the antiviral response. Not only do they express a variety of inhibitory and activating receptors to discriminate and eliminate target cells but they can also produce immunoregulatory cytokines to alert the immune system. Reciprocally, several unrelated viruses including cytomegalovirus, human immunodeficiency virus, influenza virus, and dengue virus have evolved a multitude of mechanisms to evade NK cell function, such as the targeting of pathways for NK cell receptors and their ligands, apoptosis, and cytokine-mediated signaling. The studies discussed in this article provide further insights into the antiviral function of NK cells and the pathways involved, their constituent proteins, and ways in which they could be manipulated for host benefit.


2015 ◽  
Vol 7 (6) ◽  
pp. 557-562 ◽  
Author(s):  
Timothy E. O'Sullivan ◽  
Joseph C. Sun

Immunological memory is classically regarded as an attribute of antigen-specific T and B lymphocytes of the adaptive immune system. Cells of the innate immune system, including natural killer (NK) cells, have been considered short-lived cytolytic cells that can rapidly respond against pathogens in an antigen-independent manner and then die off. However, NK cells have recently been described to possess traits of adaptive immunity, such as clonal expansion after viral antigen exposure to generate long-lived memory cells. In this review, we will discuss the current evidence for viral-induced NK cell memory in both mice and humans.


2009 ◽  
Vol 206 (7) ◽  
pp. 1495-1503 ◽  
Author(s):  
Cameron S. Brandt ◽  
Myriam Baratin ◽  
Eugene C. Yi ◽  
Jacob Kennedy ◽  
Zeren Gao ◽  
...  

Cancer development is often associated with the lack of specific and efficient recognition of tumor cells by the immune system. Natural killer (NK) cells are lymphocytes of the innate immune system that participate in the elimination of tumors. We report the identification of a tumor cell surface molecule that binds NKp30, a human receptor which triggers antitumor NK cell cytotoxicity and cytokine secretion. This previously unannotated gene belongs to the B7 family and, hence, was designated B7-H6. B7-H6 triggers NKp30-mediated activation of human NK cells. B7-H6 was not detected in normal human tissues but was expressed on human tumor cells, emphasizing that the expression of stress-induced self-molecules associated with cell transformation serves as a mode of cell recognition in innate immunity.


2008 ◽  
Vol 136 (7-8) ◽  
pp. 423-429 ◽  
Author(s):  
Vladimir Jurisic ◽  
Sladjana Stojacic-Djenic ◽  
Natasa Colovic ◽  
Gordana Konjevic

Natural killer (NK) cells are characterized by a CD3-CD16+ CD56+ immunophenotype and have a central role in the innate immune system. They are defined by their capacity to kill certain tumor-target cells or virus infected cells without prior sensitization or MHC-restriction. The activity of the NK cells is determined by the balance between activation and inhibitory receptor molecules expressed on the surface of NK cells. However, several cytokines and chemokines can significantly modulate their activity, inducing increase of NK cell activity. Immunomodulation mediated by NK cells is very important mechanism in tumor immunity, as well as in other immunodepressions of the immune system. In this study, we summarize the role of several cytokines, including IFN, IL-1, IL-2, IL-4, IL-7, IL-12 and IL-17, on NK cell function. The NK cells, after activation, depending on cytokine environment, can differentiate into NK1 cells that produce Th1 cytokine type (IFN-?, IL-2, IL-12) or NK2 cells that produce Th2 type cytokines, enhance exocytosis and release of previously formed molecules from NK cells (granzyme, perforin). We also describe that the release of cytokines and mediators show local or distance effects, or induce apoptosis (mostly by secreted TNF-?) after binding appropriated killer cell receptors from TNF receptor superfamily.


2019 ◽  
Vol 21 (3) ◽  
pp. 427-440 ◽  
Author(s):  
K. L. Markova ◽  
O. I. Stepanova ◽  
A. R. Sheveleva ◽  
N. A. Kostin ◽  
V. A. Mikhailova ◽  
...  

Regulation of angiogenesis in the utero-placental bed determines adequate trophoblast invasion, placenta formation and development, as well as successful course of pregnancy. Natural killer (NK) cells, macrophages and trophoblast have the most significant effect on angiogenesis. To date, the functions of cells participating in placenta formation have been described in detail, both individually (in vitrо) and in tissues (in situ). However, no models have yet been created that reflect the interactions of NK cells, trophoblast and endothelium during angiogenesis. It remains unclear, how each cell population contributes to placental angiogenesis regulation, and to the cross-regulation of participating cell functions. Therefore, the aim of this research was to study contact and distant effects of NK cells upon formation of tube-like structures through co-culture of endothelial and trophoblast cells influenced by various cytokines (bFGF, VEGF, PlGF, TGF-β, IL-8, IFNγ and IL-1β). Introduction of NK cells to the co-culture of endothelial and trophoblast cells under conditions of both contact and distance-dependent culturing did not change the length of tube-like structures formed by endothelial cells. During contact-dependent culturing of NK cells with co-culture of endothelial and trophoblast cells in presence of IL-1β, the length of tubule-like structures remained unchanged, compared with the length of tube-like structures formed under the same culturing conditions, but without the cytokine added. During distant culturing of NK cells with co-culture of endothelial and trophoblast cells in the presence of IL-1β, the length of tube-like structures increased as compared with those formed under the same culturing conditions but without the cytokine. During contact-dependent (but not distant) culturing of NK cells with the co-culture of endothelial and trophoblast cells in the presence of VEGF, the length of tube-like structures was greater than those formed under the same culturing conditions but without the cytokine. When used in a three-component cell system, the pro-inflammatory cytokine IFNγhad no effect upon angiogenesis. During distant (but not contact-dependent) culturing of NK cells with co-culture of endothelial and trophoblast cells in the presence of TGF-β, the length of tube-like structures was less than the length of tube-like structures formed under the same culturing conditions but without the cytokine. Under conditions of distant culturing, TGF-βtriggered a signal in NK cells that inhibited angiogenesis. Decreased length of tube-like structures under conditions of a three-component cell co-culture in the presence of the following pro-angiogenic factors was revealed: IL-8, PlGF (during contact-dependent culturing only) and bFGF (during both contact-dependent and distant culturing). Thus, the effects of cytokines upon angiogenesis in a three-component co-culture (NK cells, trophoblast and endothelium) differed from those revealed previously in single-component (endothelium only) and two-component (co-culture of endothelium and trophoblast) cell models. The results of these experiments indicated that regulation of placental cell interactions involved both cellular contacts and effects produced by cytokines.


2020 ◽  
Vol 20 (3) ◽  
pp. 202-219
Author(s):  
Dmitry Olegovich Bazhenov ◽  
Evgeniya Valerevna Khokhlova ◽  
Larisa Pavlovna Viazmina ◽  
Kseniya Nikolaevna Furaeva ◽  
Valentina Anatolievna Mikhailova ◽  
...  

Background:: Maternal natural killer cells (NK cells) are a prevailing leukocyte population in the uteroplacental bed. Current descriptions of the effect of cytokines from the placental microenvironment on the expression of receptors by trophoblast and NK cells are inadequate and contradictory. There is insufficient information about the ability of NK cells to migrate through trophoblast cells. Objective:: To assess the impact of conditioned media obtained during culturing of placentas from the first and the third trimesters of healthy pregnancies on the phenotype of trophoblast and NK cells and impact on adhesion and transmigration of NK cells through trophoblast cell layer. Results:: We established that conditioned media obtained from both first and third trimester placentas increased the intensity of CD106, CD49e, CD49a, CD31, CD51/61, and integrin β6 expression by trophoblast cells. Conditioned media obtained from first trimester placentas increased the intensity of CD11a, CD29, CD49d, CD58, CD29 expression by NK cells. The presence of conditioned media from third trimester placentas resulted in more intense CD29, CD49d, CD11a, CD29, CD49d, and CD58 expression by NK cells. Migration of NK cells through trophoblast cells in the presence of conditioned media from first trimester placentas was increased compared with the migration level in the presence of conditioned media from third trimester placentas. This may be associated with increased expression of CD18 by NK cells. Conclusion:: First trimester placental secretory products increase adhesion receptor expression by both trophoblast and NK cells. Under these conditions, trophoblast is capable of ensuring NK cell adhesion and transmigration.


1998 ◽  
Vol 188 (11) ◽  
pp. 2067-2074 ◽  
Author(s):  
Kazunori Imada ◽  
Eda T. Bloom ◽  
Hiroshi Nakajima ◽  
Judith A. Horvath-Arcidiacono ◽  
Garry B. Udy ◽  
...  

We have analyzed the immune system in Stat5-deficient mice. Although Stat5a−/− splenocytes have a partial defect in anti-CD3-induced proliferation that can be overcome by high dose interleukin (IL)-2, we now demonstrate that defective proliferation in Stat5b−/− splenocytes cannot be corrected by this treatment. Interestingly, this finding may be at least partially explained by diminished expression of the IL-2 receptor β chain (IL-2Rβ), which is a component of the receptors for both IL-2 and IL-15, although other defects may also exist. Similar to the defect in proliferation in activated splenocytes, freshly isolated splenocytes from Stat5b−/− mice exhibited greatly diminished proliferation in response to IL-2 and IL-15. This results from both a decrease in the number and responsiveness of natural killer (NK) cells. Corresponding to the diminished proliferation, basal as well as IL-2– and IL-15–mediated boosting of NK cytolytic activity was also greatly diminished. These data indicate an essential nonredundant role for Stat5b for potent NK cell–mediated proliferation and cytolytic activity.


2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Esraa Elaraby ◽  
Abdullah Imadeddin Malek ◽  
Hanan W. Abdullah ◽  
Noha Mousaad Elemam ◽  
Maha Saber-Ayad ◽  
...  

Natural killer cells (NK cells) are a crucial constituent of the innate immune system as they mediate immunity against viruses, bacteria, parasites, and most importantly, tumor cells. The exact mechanism of how the innate immune system and specifically NK cells interact with cancer cells is complex and is yet to be understood. Several factors that constitute the tumor microenvironment (TME) such as hypoxia and TGF-β are believed to play a role in the complex physiological reaction of NK cells to tumor cells. On the other hand, several risk factors are implicated in the development and progression of breast cancer, most importantly: obesity. Cytokines released from adipose tissue such as adipokines, leptin, and resistin, among others, are also believed to facilitate tumor progression. In this study, we aimed to build a triad of breast cancer, obesity, and NK cell dysfunction to elucidate a link between these pillars on a cellular level. Directing efforts towards solidifying the link between these factors will help in designing a targeted immunotherapy with a low side-effect profile that can revolutionize breast cancer treatment and improve survival in obese patients.


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