scholarly journals Virus-specific NK cell memory

2021 ◽  
Vol 218 (4) ◽  
Author(s):  
Sam Sheppard ◽  
Joseph C. Sun
Keyword(s):  
Nk Cells ◽  
Cytomegalovirus Infection ◽  
Cytokine Production ◽  
Nk Cell ◽  
Transformed Cells ◽  
Surface Receptors ◽  
Clonal Proliferation ◽  
Cell Clones ◽  
Memory Pool ◽  
Infected Cells

NK cells express a limited number of germline-encoded receptors that identify infected or transformed cells, eliciting cytotoxicity, effector cytokine production, and in some circumstances clonal proliferation and memory. To maximize the functional diversity of NK cells, the array and expression level of surface receptors vary between individual NK cell “clones” in mice and humans. Cytomegalovirus infection in both species can expand a population of NK cells expressing receptors critical to the clearance of infected cells and generate a long-lived memory pool capable of targeting future infection with greater efficacy. Here, we discuss the pathways and factors that regulate the generation and maintenance of effector and memory NK cells and propose how this understanding may be harnessed therapeutically.

scholarly journals DNAM-1 controls NK cell activation via an ITT-like motif

2015 ◽  
Vol 212 (12) ◽  
pp. 2165-2182 ◽  
Author(s):  
Zhanguang Zhang ◽  
Ning Wu ◽  
Yan Lu ◽  
Dominique Davidson ◽  
Marco Colonna ◽  
...  
Keyword(s):  
Nk Cells ◽  
Cd8 T Cells ◽  
Actin Polymerization ◽  
Cell Activation ◽  
Cytokine Production ◽  
Nk Cell ◽  
Phosphatidylinositol 3 Kinase ◽  
Specific Memory ◽  
Downstream Effectors ◽  
Infected Cells

DNAM-1 (CD226) is an activating receptor expressed on natural killer (NK) cells, CD8+ T cells, and other immune cells. Upon recognition of its ligands, CD155 and CD112, DNAM-1 promotes NK cell–mediated elimination of transformed and virus-infected cells. It also has a key role in expansion and maintenance of virus-specific memory NK cells. Herein, the mechanism by which DNAM-1 controls NK cell–mediated cytotoxicity and cytokine production was elucidated. Cytotoxicity and cytokine production triggered by DNAM-1 were mediated via a conserved tyrosine- and asparagine-based motif in the cytoplasmic domain of DNAM-1. Upon phosphorylation by Src kinases, this motif enabled binding of DNAM-1 to adaptor Grb2, leading to activation of enzymes Vav-1, phosphatidylinositol 3′ kinase, and phospholipase C-γ1. It also promoted activation of kinases Erk and Akt, and calcium fluxes. Although, as reported, DNAM-1 promoted adhesion, this function was signal-independent and insufficient to promote cytotoxicity. DNAM-1 signaling was also required to enhance cytotoxicity, by increasing actin polymerization and granule polarization. We propose that DNAM-1 promotes NK cell activation via an immunoreceptor tyrosine tail (ITT)–like motif coupling DNAM-1 to Grb2 and other downstream effectors.

scholarly journals Natural killer cells: Biology, functions and clinical relevance

2010 ◽  
Vol 63 (1-2) ◽  
pp. 91-97 ◽  
Author(s):  
Svetlana Vojvodic ◽  
Stevan Popovic
Keyword(s):  
Natural Killer Cells ◽  
Cell Surface ◽  
Nk Cells ◽  
Natural Killer ◽  
Clinical Relevance ◽  
Nk Cell ◽  
Transformed Cells ◽  
Cell Surface Receptors ◽  
Killer Cells ◽  
Surface Receptors

Introduction. Natural Killer cells (NK cells) represent the subset of peripheral lymphocytes that play critical role in the innate immune response to virus-infected and tumor transformed cells. Lysis of NK sensitive target cells could be mediated independently of antigen stimulation and without requirement of peptide presentation by the major histocompatibility complex (MHC) molecules. NK cell activity and functions are controlled by a considerable number of cell surface receptors, which exist in both inhibitory and activating isoforms. There are several groups of NK cell surface receptors: 1) killer immunoglobulin like receptors-KIR, 2) C-type lectin receptors,3)natural citotoxicity receptors-NCR and 4) Toll-like receptors-TLR. Functions of NK receptors. Defining the biology of NK cell surface receptors has contributed to the concept of the manner how NK cells selectively recognize and lyse tumor and virally infected cells while sparing normal cells. Further, identification of NK receptor ligands and their expression on the normal and transformed cells has led to the development of clinical approaches to manipulating receptor/ligand interactions that showed clinical benefit. NK cells are the first lymphocyte subset that reconstitute the peripheral blood following allogeneic HSCT and multiple roles for alloreactive donor NK cells have been demonstrated, in diminishing Graft vs. Host Disease (GvHD) through selective killing recipient dendritic cells, prevention of graft rejection by killing recipient T cells and participation in Graft vs. Leukaemia (GvL) effect through destruction of residual host tumor cells. Conclusion. Besides their role in HSCT, NK cell receptors have an important clinical relevance that reflects from the fact that they play a crucial role in the development of some diseases as well as in possibilities of managing all NK receptors through selective expansion and usage of NK cells in cancer immunotherapy.

scholarly journals LAG3 is a Central Regulator of NK Cell Cytokine Production

2020 ◽  
Author(s):  
Sriram Narayanan ◽  
Patricia J. Ahl ◽  
Veonice Au Bijin ◽  
Nivashini Kaliaperumal ◽  
Seng Gee Lim ◽  
...  
Keyword(s):  
Nk Cells ◽  
Cytokine Production ◽  
Viral Infections ◽  
Nk Cell ◽  
Chronic Viral Hepatitis ◽  
Negative Regulator ◽  
Surface Receptors ◽  
Healthy Donors ◽  
The Impact

AbstractNatural killer (NK) cells are innate effectors, which play a crucial role in controlling viral infections. Administration of IFN-α has shown promising results as a therapeutic, controlling HIV, and chronic viral hepatitis. However the downstream mechanisms by which IFN-α mediates its anti-viral effects is largely unknown. In this investigation, we evaluated the impact of IFN-α on peripheral blood NK cells from healthy donors. High dimensional flow cytometry analysis of NK cell surface receptors following exposure to IFN-α showed an increased expression of the check point inhibitor LAG3. Further characterization revealed that LAG3 was expressed in a subset of NK cells with high expression of activation and maturation markers. Assessment of metabolic pathways showed that LAG3+ NK cells had enhanced rates of glycolysis and glycolytic capacity, suggesting that it is a primed effector subset with enhanced glucose metabolism. Inhibition of LAG3 on NK cells using antibody in vitro resulted in a profound increase in secretion of cytokines IFN-γ, TNF-α, MIP-1α and MIP-1β, without affecting the cytotoxic activity. Taken together, these results showed that LAG3 is a negative regulator of cytokine production by mature NK cells.

scholarly journals Immunosurveillance of Cancer and Viral Infections with Regard to Alterations of Human NK Cells Originating from Lifestyle and Aging

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 557
Author(s):  
Xuewen Deng ◽  
Hiroshi Terunuma ◽  
Mie Nieda
Keyword(s):  
Nk Cells ◽  
Viral Infections ◽  
Nk Cell ◽  
Healthy Lifestyle ◽  
Cell Activity ◽  
Nk Cell Activity ◽  
Effector Cells ◽  
Cell Dysfunction ◽  
Forest Bathing ◽  
Infected Cells

Natural killer (NK) cells are cytotoxic immune cells with an innate capacity for eliminating cancer cells and virus- infected cells. NK cells are critical effector cells in the immunosurveillance of cancer and viral infections. Patients with low NK cell activity or NK cell deficiencies are predisposed to increased risks of cancer and severe viral infections. However, functional alterations of human NK cells are associated with lifestyles and aging. Personal lifestyles, such as cigarette smoking, alcohol consumption, stress, obesity, and aging are correlated with NK cell dysfunction, whereas adequate sleep, moderate exercise, forest bathing, and listening to music are associated with functional healthy NK cells. Therefore, adherence to a healthy lifestyle is essential and will be favorable for immunosurveillance of cancer and viral infections with healthy NK cells.

scholarly journals NK Cell Regulation in Cervical Cancer and Strategies for Immunotherapy

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3104
Author(s):  
Adriana Gutiérrez-Hoya ◽  
Isabel Soto-Cruz
Keyword(s):  
Cervical Cancer ◽  
Nk Cells ◽  
Nk Cell ◽  
Hpv Infection ◽  
Cytolytic Activity ◽  
Cellular Immunotherapy ◽  
Antigen Receptors ◽  
Cytokines And Chemokines ◽  
Hpv Status ◽  
Infected Cells

Cervical cancer is one of the most prevalent gynaecological malignancies worldwide and is related to human papillomavirus (HPV) infection, viral persistence, progression, and invasion. Therefore, the immune response is linked to HPV status. Natural killer (NK) cells play a central role against virus-infected cells and tumours through a delicate balance between activating and inhibitory receptors and secretion of cytokines and chemokines. These cells also play a crucial role in tumour immunosurveillance. For these reasons, there is growing interest in harnessing NK cells as an immunotherapy for cervical cancer. These studies are diverse and include many strategies such as transferring activated autologous or allogeneic NK cells, improving the activation and cytolytic activity of NK cells using cytokines or analogues and modifying chimeric antigen receptors to increase specificity and targeting NK cells. However, research regarding the application of NK cells in immunotherapy is limited. This article focuses on recent discoveries about using NK cells to prevent and treat cervical cancer and the possibility of cellular immunotherapy becoming one of the best strategies to exploit the immune system to fight tumours.

scholarly journals Natural Killer Cells in the Malignant Niche of Multiple Myeloma

2022 ◽  
Vol 12 ◽  
Author(s):  
Ondrej Venglar ◽  
Julio Rodriguez Bago ◽  
Benjamin Motais ◽  
Roman Hajek ◽  
Tomas Jelinek
Keyword(s):  
Multiple Myeloma ◽  
Nk Cells ◽  
Natural Killer ◽  
Defense Mechanisms ◽  
Hematological Malignancies ◽  
Cell Function ◽  
Nk Cell ◽  
Current Knowledge ◽  
Suppressor Activity ◽  
Infected Cells

Natural killer (NK) cells represent a subset of CD3- CD7+ CD56+/dim lymphocytes with cytotoxic and suppressor activity against virus-infected cells and cancer cells. The overall potential of NK cells has brought them to the spotlight of targeted immunotherapy in solid and hematological malignancies, including multiple myeloma (MM). Nonetheless, NK cells are subjected to a variety of cancer defense mechanisms, leading to impaired maturation, chemotaxis, target recognition, and killing. This review aims to summarize the available and most current knowledge about cancer-related impairment of NK cell function occurring in MM.

scholarly journals The phenotype of NK-cells in the dynamics of the post-operative period in patients with peritonitis in depending on the outcome of the disease

2019 ◽  
Vol 9 (3-4) ◽  
pp. 539-548
Author(s):  
A. A. Savchenko ◽  
A. G. Borisov ◽  
I. V. Kudryavcev ◽  
V. D. Belenjuk
Keyword(s):  
Nk Cells ◽  
Postoperative Period ◽  
Peripheral Blood ◽  
Nk Cell ◽  
Favorable Outcome ◽  
Control Group ◽  
Preoperative Period ◽  
Surface Receptors ◽  
Post Surgery ◽  
Purulent Peritonitis

Our study was aimed at investigating dynamic phenotype pattern of peripheral blood NK cells in patients with widespread purulent peritonitis (WPP) during postoperative period depending on disease outcome. A total of 48 patients aged 30–63 with acute surgical diseases and abdominal injuries complicated by WPP were examined. Blood sampling was performed before surgery (preoperative period) as well as on day 7, 14 and 21 during postoperative period. 40 apparently healthy age-matched subjects were included in control group. Peripheral blood NK cell phenotyping was performed by using flow cytometry with directly immunofluorescently tagged antibodies. Mean fluorescence intensity was measured to estimate expression levels of NK cell surface receptors was measured. It was found that in patients with a favorable WPP outcome during preoperative period the percentage of mature NK cells was decreased that was restored by the end of the postoperative period (21 days post-surgery) due to elevated mature, cytotoxic and cytokine-producing NK cell subsets. In addition, percentage of CD11b-positive NK cell subsets was increased upon favorable outcome by the end of postoperative period as well as frequency of CD57-positive NK cells relative to the preoperative period. However, frequency of mature NK cells with unfavorable WPP outcome vs. control vs. favorable outcome was decreased during preoperative and entire postoperative period. Moreover, amount of cytotoxic NK cells was elevated during examination period upon unfavorable WPP outcome. Further, percentage of mature CD11b-positive NK cells in this patient cohort was decreased during preoperative period and post-surgery. Percentage of CD57-positive NK cells was decreased during entire postoperative period in patients with unfavorable vs. favorable outcome vs. control group. At the same time, patients with unfavorable outcome of this infectious-inflammatory disease were shown to display upregulated expression of CD28 and CD57 markers on NK cells. such features identified in phenotype of peripheral blood NK cells in patients with unfavorable WPP outcome reflect abnormal mechanisms in NK cell maturation and migration, which, in turn, determines disturbance in events regulating acute inflammatory reaction in WPP. 

scholarly journals Recognition of virus-infected cells by natural killer cell clones is controlled by polymorphic target cell elements.

1993 ◽  
Vol 178 (3) ◽  
pp. 961-969 ◽  
Author(s):  
M S Malnati ◽  
P Lusso ◽  
E Ciccone ◽  
A Moretta ◽  
L Moretta ◽  
...  
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Natural Killer ◽  
Target Cell ◽  
Nk Cell ◽  
Class I ◽  
Target Cells ◽  
Cell Recognition ◽  
Infected Cells ◽  
Nk Cell Recognition

Natural killer (NK) cells provide a first line of defense against viral infections. The mechanisms by which NK cells recognize and eliminate infected cells are still largely unknown. To test whether target cell elements contribute to NK cell recognition of virus-infected cells, human NK cells were cloned from two unrelated donors and assayed for their ability to kill normal autologous or allogeneic cells before and after infection by human herpesvirus 6 (HHV-6), a T-lymphotropic herpesvirus. Of 132 NK clones isolated from donor 1, all displayed strong cytolytic activity against the NK-sensitive cell line K562, none killed uninfected autologous T cells, and 65 (49%) killed autologous T cells infected with HHV-6. A panel of representative NK clones from donors 1 and 2 was tested on targets obtained from four donors. A wide heterogeneity was observed in the specificity of lysis of infected target cells among the NK clones. Some clones killed none, some killed only one, and others killed more than one of the different HHV-6-infected target cells. Killing of infected targets was not due to complete absence of class I molecules because class I surface levels were only partially affected by HHV-6 infection. Thus, target cell recognition is not controlled by the effector NK cell alone, but also by polymorphic elements on the target cell that restrict NK cell recognition. Furthermore, NK clones from different donors display a variable range of specificities in their recognition of infected target cells.

scholarly journals Mouse Ly49G2+ NK cells dominate early responses during both immune reconstitution and activation independently of MHC

Blood ◽  
2011 ◽  
Vol 117 (26) ◽  
pp. 7032-7041 ◽  
Author(s):  
Isabel Barao ◽  
Maite Alvarez ◽  
Erik Ames ◽  
Mark T. Orr ◽  
Heather E. Stefanski ◽  
...  
Keyword(s):  
Nk Cells ◽  
Mhc Class I ◽  
Cytomegalovirus Infection ◽  
Immune Reconstitution ◽  
Nk Cell ◽  
Rapid Expansion ◽  
Normal Pattern ◽  
Mouse Cytomegalovirus ◽  
Single Positive ◽  
Independent Expansion

Abstract Natural killer (NK) cell subsets can be defined by the differential expression of inhibitory receptors for MHC class I molecules. Early after congenic HSCT, we found that Ly49G2high single-positive NK cells repopulated, displayed an activated phenotype, and were highly cytolytic. Over time, this subset was replaced with NK cells with a normal pattern of Ly49 expression. Treatment of mice with IL-2 also resulted in the rapid expansion of these Ly49G2high single-positive NK cells. Only the Ly49g (Klra7) Pro1 transcript was highly induced in both HSCT- and IL-2–treated recipients. MHC-independent expansion of the Ly49G2+ subset was also observed after Listeria monocytogenes or mouse cytomegalovirus infection. Our data indicate that during reconstitution after HSCT and various activation stimuli, Ly49G2+ NK cells represent the “first-responder” NK cells, which occur independently of NK-cell licensing via Ly49-MHC interactions. These data suggest that the inhibitory Ly49G2 receptor represents an activation marker on mouse NK cells under various conditions.

scholarly journals Cytomegalovirus-Driven Adaption of Natural Killer Cells in NKG2Cnull Human Immunodeficiency Virus-Infected Individuals

Viruses ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 239 ◽  
Author(s):  
Emilie M. Comeau ◽  
Kayla A. Holder ◽  
Neva J. Fudge ◽  
Michael D. Grant
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cell Differentiation ◽  
Hiv Infection ◽  
Nk Cells ◽  
Natural Killer ◽  
Cytokine Production ◽  
Zinc Finger Protein ◽  
Nk Cell ◽  
Immunodeficiency Virus ◽  
Nk Cell Differentiation

Expansion of natural killer (NK) cells expressing NKG2C occurs following human cytomegalovirus (HCMV) infection and is amplified by human immunodeficiency virus (HIV) co-infection. These NKG2C-expressing NK cells demonstrate enhanced CD16-dependent cytokine production and downregulate FcεRIγ and promyelocytic leukemia zinc finger protein (PLZF). Lacking NKG2C diminishes resistance to HIV infection, but whether this affects NK cell acquisition of superior antibody-dependent function is unclear. Therefore, our objective was to investigate whether HCMV-driven NK cell differentiation is impaired in NKG2Cnull HIV-infected individuals. Phenotypic (CD2, CD16, CD57, NKG2A, FcεRIγ, and PLZF expression) and functional (cytokine induction and cytotoxicity) properties were compared between HIV–infected NKG2Cnull and NKG2C-expressing groups. Cytokine production was compared following stimulation through natural cytotoxicity receptors or through CD16. Cytotoxicity was measured by anti-CD16-redirected lysis and by classical antibody-dependent cell-mediated cytotoxicity (ADCC) against anti-class I human leukocyte antigen (HLA) antibody-coated cells. Our data indicate highly similar HCMV-driven NK cell differentiation in HIV infection with or without NKG2C. While the fraction of mature (CD57pos) NK cells expressing CD2 (p = 0.009) or co-expressing CD2 and CD16 (p = 0.03) was significantly higher in NKG2Cnull HIV-infected individuals, there were no significant differences in NKG2A, FcεRIγ, or PLZF expression. The general phenotypic and functional equivalency observed suggests NKG2C-independent routes of HCMV-driven NK cell differentiation, which may involve increased CD2 expression.

Sign in / Sign up

Export Citation Format

Share Document