Role Of Natural Killer Research Articles

A think tank of TINK/TANKs: tumor-infiltrating/tumor-associated natural killer cells in tumor progression and angiogenesis.

Tumor-infiltrating leukocytes are often induced by the cancer microenvironment to display a protumor, proangiogenic phenotype. This “polarization” has been described for several myeloid cells, in particular macrophages. Natural killer (NK) cells represent another population of innate immune cells able to infiltrate tumors. The role of NK in tumor progression and angiogenesis has not yet been fully investigated. Several studies have shown that tumor-infiltrating NK (here referred to as “TINKs”) and tumor-associated NK (altered peripheral NK cells, which here we call “TANKs”) are compromised in their ability to lysew tumor cells. Recent data have suggested that they are potentially protumorigenic and can also acquire a proangiogenic phenotype. Here we review the properties of TINKs and TANKs and compare their activities to that of NK cells endowed with a physiological proangiogenic phenotype, in particular decidual NK cells. We speculate on the potential origins of TINKs and TANKs and on the immune signals involved in their differentiation and polarization. The TINK and TANK phenotype has broad implications in the immune response to tumors, ranging from a deficient control of cancer and cancer stem cells to an altered crosstalk with other relevant players of the immune response, such as dendritic cells, to induction of cancer angiogenesis. With this recently acquired knowledge that has not yet been put into perspective, we point out new potential avenues for therapeutic intervention involving NK cells as a target or an ally in oncology.

Natural Killer Cell Subsets Differentially Reject Embryonic Stem Cells Based on Licensing

Embryonic stem cells (ESC) and induced pluripotent stem cells provide great promise to the future of medicine. Because immune rejection represents a major obstacle to the success of all stem cell-based therapies, many recent studies have sought to determine the key immune mediators involved in ESC rejection. The role of natural killer (NK) cells and specifically the role of NK cell licensing is not well understood in ESC rejection. Mouse or human ESCs were subjected to cytotoxicity assays involving their respective species-matched activated NK cells. Mouse ESCs were then transplanted to allogeneic recipients after depletion of NK cell subsets in the host. ESC engraftment was analyzed by bioluminescent imaging. Depletion of all NK cells in vivo resulted in the greatest amount of ESC engraftment, confirming a role for NK cells in ESC rejection. Importantly, depletion of the Ly49C/I or Ly49G2 NK cell subsets resulted in differential ESC engraftment and rejection. This indicates that NK cell rejection of allogeneic ESC is highly differential based on the presence of licensed NK cells. Blocking NKG2D in vitro resulted in less killing of mESC by allogeneic NK cells, indicating NKG2D is a likely mechanism for NK-mediated killing of mESC. In this study, we show that expression of inhibitory Ly49s correlates with the ability of NK cells to kill murine ESC in an NKG2D-dependent manner. This further suggests that the rejection of similar stem cell transplants in humans will be dependent upon the presence of licensed NK cells.

Control of acute dengue virus infection by natural killer cells.

Dengue fever is the most important arthropod-borne viral disease worldwide, affecting 50–100 million individuals annually. The clinical picture associated with acute dengue virus (DENV) infections ranges from classical febrile illness to life-threatening disease. The innate immunity is the first line of defense in the control of viral replication. This review will examine the particular role of natural killer (NK) cells in DENV infection. Over recent years, our understanding of the interplay between NK cells and viral pathogenesis has improved significantly. NK cells express an array of inhibitory and activating receptors that enable them to detect infected targets while sparing normal cells, and to recruit adaptive immune cells. To date, the exact mechanism by which NK cells may contribute to the control of DENV infection remains elusive. Importantly, DENV has acquired mechanisms to evade NK cell responses, further underlining the relevance of these cells in pathophysiology. Hence, understanding how NK cells affect the outcome of DENV infection could benefit the management of this acute disease.

Abstract 641: Interleukin-15 Plays a Role in Atherosclerosis Through Effects on Multiple Inflammatory Cells in ApoE-/- Mice

Objective: Interleukin (IL)-15 is a pro-inflammatory cytokine which is essential for the survival and maturation of natural killer (NK) and CD8+ T cells and has recently been reported to directly activate macrophages. In the present study, we used IL-15 overexpressing and IL-15 knockout mice to determine its effect on atherosclerosis in apolipoprotein E knockout (apoE-/-) mice. Approach and Results: Deficiency of IL-15 reduced atherosclerosis while overexpression of IL-15 increased atherosclerosis despite opposite effects on plasma lipoprotein cholesterol levels. Genetic ablation of IL-15 in apoE-/- mice resulted in a lack of NK cells and reduced populations of monocytes and CD8+ T cells, whereas overexpression of IL-15 had the opposite effects. CD8+ T cells were detected in atherosclerotic plaques from apoE-/- mice, were increased in plaques from il-15TgapoE-/- mice and were virtually absent from plaques from il15-/- apoE-/- mice. To test the role of NK, NKT and activated CD8+ T cells in atherosclerosis, NK1.1+ cells were immuno-depleted from apoE-/- mice. Atherosclerosis was reduced but to a lesser extent than in age matched il15-/- apoE-/- mice. Plaques from these mice, however, were almost devoid of CD8+ T cells. ApoE-/- mice that were heterozygous for IL-15 (il15+/-apoE-/-) exhibited normal levels of NK, NKT, CD8T cells and monocytes however atherosclerosis was reduced by 40-50 % compared to control apoE-/- mice. This suggested that IL-15 also affects atherosclerosis through NK/NKT and CD8+ T cell independent pathways. Treatment of macrophages with recombinant IL-15 in vitro induced inflammatory cytokines and foam cell formation. Furthermore, reduced levels of MCP-1 and CD11b immune-reactivity were detected in plaques from il15-/- apoE-/- compared to control apoE-/- mice. Conclusions: IL-15 plays a significant role in promoting atherosclerosis through pathways affecting multiple inflammatory cells including the survival/recruitment of NK, NKT and CD8+ T cells, the modulation of monocyte levels, and direct activation of macrophages.

Crosstalk between adipocytes and immune cells in adipose tissue inflammation and metabolic dysregulation in obesity.

Recent findings, notably on adipokines and adipose tissue inflammation, have revised the concept of adipose tissues being a mere storage depot for body energy. Instead, adipose tissues are emerging as endocrine and immunologically active organs with multiple effects on the regulation of systemic energy homeostasis. Notably, compared with other metabolic organs such as liver and muscle, various inflammatory responses are dynamically regulated in adipose tissues and most of the immune cells in adipose tissues are involved in obesity-mediated metabolic complications, including insulin resistance. Here, we summarize recent findings on the key roles of innate (neutrophils, macrophages, mast cells, eosinophils) and adaptive (regulatory T cells, type 1 helper T cells, CD8 T cells, B cells) immune cells in adipose tissue inflammation and metabolic dysregulation in obesity. In particular, the roles of natural killer T cells, one type of innate lymphocyte, in adipose tissue inflammation will be discussed. Finally, a new role of adipocytes as antigen presenting cells to modulate T cell activity and subsequent adipose tissue inflammation will be proposed.

High CD56++CD16- natural killer (NK) cells among suboptimal immune responders after four years of suppressive antiretroviral therapy in an African adult HIV treatment cohort

BackgroundUp to 40% of HIV-infected individuals receiving Highly Active Antiretroviral Therapy (HAART) have poor CD4+ T-cell recovery. The role of natural killer (NK) cells in immune recovery during HAART is not well understood. We described the profiles of NK cell subsets and their expression of activating receptor, NKG2D and cytotoxicity receptor NKp46 among suboptimal immune responders to despite four years of suppressive HAART.MethodsA case control study utilized frozen peripheral blood mononuclear cells (PBMC) from a cohort of HIV-infected adults that initiated HAART in 2004/5, at CD4 < 200 cells/μl. Cases were ‘suboptimal’ responders; patients within the lowest quartile of CD4+ T-cell reconstitution, with a median CD4 count increase of 129 (-43-199) cells/μl (difference between CD4 count at baseline and after 4 years of HAART) and controls were ‘super-optimal’ responders; patients within the highest quartile of CD4 T-cell reconstitution with a median CD4 count increase of 528 (416-878) cells/μl). Expression of NK cell lineage markers (CD56+/-CD16+/-) and receptors NKG2D and NKp46, was measured among PBMC from 29 cases of ‘suboptimal’ responders’ and 23 controls of ‘super-optimal responders’, and compared among ‘suboptimal’ and ‘super-optimal’ responders. NK cell populations were compared using the Holm Sidak multiple comparison test and p values < 0.05 were considered statistically significant. Data was analyzed using FLOWJO and GraphPad Prism 6.Results‘Suboptimal responders’ had a higher proportion of cytokine producing CD56++CD16+/- (CD56bri) NK cells than the ‘super-optimal responders’ p = 0.017, and CD56neg NK cells were lower among suboptimal than super-optimal responders (p = 0.007). The largest NK cell subset, CD56dim, was comparable among suboptimal responders and ‘super-optimal immune responders’. Expression of NKG2D and NKp46 receptors on NK cell subsets (CD56bri, CD56neg and CD56dim), was comparable among ‘suboptimal’ and ‘super-optimal’ immune responders.ConclusionsThe pro-inflammatory CD56++CD16-- NK cells were higher among ‘suboptimal’ responders relative to ‘super-optimal’ responders, despite four years of suppressive HAART. Alteration of NK cell populations could inhibit host immune responses to infections among suboptimal responders. We recommend further analysis of NK cell function among suboptimal immune responders in order to inform targeted interventions to optimize immune recovery among HAART-treated adults.

Increased activated natural killer T cells in the liver of patients with advanced stage primary biliary cirrhosis.

Although growing evidence suggests a major role for T cells in the pathogenesis of primary biliary cirrhosis (PBC), the roles of natural killer (NK) and natural killer T (NKT) cells, which predominate in the liver, in the pathogenesis of PBC remain unclear. We investigated the status of NK and NKT cells in the liver and peripheral blood samples obtained from 11 patients with asymptomatic PBC diagnosed as stage I or II (early PBC) and 7 patients with symptomatic PBC who underwent liver transplantation (advanced PBC) using flow cytometry and immunohistochemical staining. The proportions of NK and NKT cells were significantly decreased in the liver of patients with early PBC compared with normal donors. However, the proportion of CD56+ NKT cells was increased in the liver of patients with advanced PBC. Moreover, the proportion of activated Fas ligand (FasL)-positive NKT cells was significantly increased in the liver of patients with advanced PBC compared with early PBC (P=0.013). We also found increased expression of FasL on lymphocytes infiltrating around the injured bile duct in advanced PBC using immunohistochemical staining. Our results suggest that activated NKT cells may contribute to the biliary epithelial cell death resulting in the progression of PBC.

Diverse Roles of Natural Killer T Lymphocytes in Liver and Spleen in Mice with Experimental Autoimmune Uveitis

Natural killer T lymphocytes (NKT cells) have diverse roles in different organs. However, it is still unclear whether NKT cells play different roles in the liver and spleen in mice with experimental autoimmune uveitis. In the present study, we explored their diverse roles of NKT cells in the liver and spleen and found that liver-derived NKT cells could efficiently inhibit Th1 and Th17 differentiation, whereas the function of spleen-derived NKT cells was less potent. Meanwhile, the occurrence of the peak ratios of NKT cells/T cells in the spleen and liver was markedly asynchronous after immunization. Moreover, different methods of immunization could result in different immune responses in mice. Furthermore, the memory response was also found in the generation of NKT cells in mice when they received the same antigen. These results indicate that the functional roles of NKT cells possess diversity in the spleen and liver in mice with experimental autoimmune uveitis.

Natural Killer Cell Death Mediated By NKG2D-Trogocytosis

IntroductionThe activating receptor, NKG2D, plays crucial role in natural killer (NK) cell-mediated effector function. NKG2D is involved not only in host defense against tumor and viral infection, but also in autoimmune diseases by recognizing stress-induced self-ligands (NKG2DLs). However, the negative feedback regulation of NKG2D has not been fully understood. It has been reported that NK cells undergo rapid apoptosis upon interaction with NK-sensitive tumor cells, suggesting that activation-induced NK cell death can be triggered in certain situations. In this study, we aimed to elucidate underlying mechanism of NK cell death, especially focused on NKG2D-NKG2DLs interaction. MethodsNK cells were purified from splenocytes of C57BL/6, perforin-/-, and DAP10-/-/12-/- mice, and cultured with rhIL-2 (1000 U/ml) for 5 days. We used these IL-2-activated NK cells as effector cells and three target cell lines: mouse T cell lymphoma RMA cells (RMA), RMA lacking MHCI expression (RMA-S), and RMA stably expressing an NKG2DL, Rae-1δ (RMA/Rae-1δ). CFSE-labeled NK cells were co-cultured with target cells for 2 hours, and stained with anti-NK1.1 mAb propidium iodide (PI). The percentage of PI-positive cells within CFSE+ NK1.1+ population was measured by flowcytometry. The cell surface expression of Rae-1 on NK cells after co-culture with target cells was evaluated by flowcytometry and confocal microscopy. ResultsNK cells from WT mice rapidly underwent cell death when co-cultured with Rae-1δ, but not with RMA or RMA-S, suggesting that NKG2D-Rae-1 interaction is involved in NK cell death. NK cells from perforin-/-, and DAP10-/-/12-/- mice did not undergo cell death, highlighting the importance of the NKG2D pathway for NK cell death. However, cross-linking of NKG2D receptor failed to induce NK cell death. To understand underlying the mechanism of NK cell death, we evaluated the cell surface expression of NKG2DLs on NK cells after co-culture with tumor cells. We found that cell surface expression of Rae-1 on NK cells was remarkably induced after co-culture with RMA/Rae-1δ, but no with RMA or RMA-S, implying that these Rae-1-positive NK cells may be lysed by NK cells through NKG2D-induced perforin pathway. The cell surface induction of Rae-1 on NK cells was very rapid (within 5min), and it occurred cell-cell contact dependent manner. Interestingly, NK cells from C57/BL6 mice rapidly became BALB/c allele Rae-1γ-positive after co-culture with RMA/Rae-1γ, indicating that NK cells acquire tumor-derived Rae-1. Consistently, acquisition of Rae-1 by NK cells was confirmed by confocal microscopy. Therefore, NK cells rapidly dress tumor-derived Rae-1 after interaction with tumor cells through intercellular membrane transfer, namely trogocytosis. Trogocytosis of Rae-1 was significantly inhibited in NK cells from DAP10-/-/12-/- mice and by chemical inhibitors of PI3K and Syk, indicating that it requires NKG2D-signaling. To confirm whether Rae-1-dressed NK cells can be recognized and lysed by other NK cells, we used sort-purified Rae-1-dressed NK cells as target cells. Rae-1-dressed NK cells were lysed by WT NK cell in an E/T-ratio dependent manner through NKG2D-induced perforin pathway. Furthermore, adoptively transferred Rae-1-dressed NK cells were significantly eliminated in Rag-1-deficient mice, indicating that Rae-1-dressed NK cells are also recognized and lysed in vivo. ConclusionUpon interaction with NKG2DLs-expressing tumor cells NK cells rapidly dress tumor-derived NKG2DLs, and subsequently undergo fratricide. Our results provide novel insights into activation-induced NK cell death via dynamic intercellular communications. Disclosures:No relevant conflicts of interest to declare.

Detection of Natural Killer T Cells in Mice Infected withRickettsia conorii

Little information is available regarding the role of natural killer T (NKT) cells during the early stage of Rickettsia conorii infection. Herein, C3H/HeN mice were infected with the Malish 7 strain of R. conorii. Splenocytes from these mice were analysed in the early stage of the infection by flow cytometry and compared with uninfected controls. Our results showed an increase in NKT cells in infected mice. Additionally, NKT interleukin (IL)-17(+) cells increased three days after infection, together with a concurrent decrease in the relative amount of NKT interferon (IFN)-γ(+) cells. We also confirmed a higher amount of NK IFN-γ(+) cells in infected mice. Taken together, our data showed that NKT cells producing Il-17 increased during the early stage of rickettsial infection. These results suggest a connection between IL-17(+) NKT cells and vasculitis, which is the main clinical symptom of rickettsiosis.

Role of Natural Killer and Gamma-Delta T cells in West Nile Virus Infection

Natural Killer (NK) cells and Gamma-delta T cells are both innate lymphocytes that respond rapidly and non-specifically to viral infection and other pathogens. They are also known to form a unique link between innate and adaptive immunity. Although they have similar immune features and effector functions, accumulating evidence in mice and humans suggest these two cell types have distinct roles in the control of infection by West Nile virus (WNV), a re-emerging pathogen that has caused fatal encephalitis in North America over the past decade. This review will discuss recent studies on these two cell types in protective immunity and viral pathogenesis during WNV infection.

An evaluation of the role of NKG2C+ natural killer cells in protection from cytomegalovirus DNAemia early following allogeneic stem cell transplantation

The role of natural killer (NK) cells in affording protection against human cytomegalovirus (CMV) in allogeneic stem cell transplant recipients is largely unknown. The current study was aimed at determining whether NKG2C+ NK cells confer protection from CMV DNAemia early following transplantation in patients lacking mono and polyfunctional CMV pp65 and IE-1-specific CD4+ and CD8+ T-cell responses, as measured by flow cytometry for intracellular cytokine staining. Fourteen out of the 36 patients included in this study developed CMV DNAemia between days +30 and +60 after transplant. Three patients did so after day +60. Peripheral blood levels of CD56(bright) CD16(-/low) and CD56(dim) CD16+ NKG2C+ NK cells measured at day +30 and at day +60 in patients who had or had not subsequent CMV DNAemia did not differ significantly. In addition, no significant correlation was found between CD56(bright) CD16(-/low) (σ = -0.229; P = 0.39) and CD56(dim) CD16+ (σ = -0.285; P = 0.28) NKG2C+ NK-cell levels and initial plasma CMV DNA loads. In summary, the data presented do not support a direct implication of NKG2C+ NK cells in preventing the development of CMV DNAemia or modulating the magnitude of CMV replication at early stages during episodes of CMV DNAemia in allogeneic stem cell transplant patients with unreconstituted CMV-specific T-cell responses.

Dynamics of natural killer cell responses to hepatitis delta virus infection during the course of interferon alpha treatment (P6070)

Abstract Infection with the hepatitis delta virus (HDV) causes the most severe form of viral hepatitis. 15-20 million people are chronically infected with HDV. Hepatitis delta is believed to be an immune-mediated disease however adaptive immune responses against HDV are hardly detectable. This suggests a possible role of natural killer (NK) cells in the pathogenesis of HDV infection. To study this, we collected blood samples from 34 patients with hepatitis delta, 16 out of which were sampled during antiviral treatment with pegylated interferon alpha (peg-IFNalpha). Expression levels of activation and inhibitory NK cell receptors and multi-functional NK cell responses were assessed using 15-color flow cytometry. HDV infected patients exhibited higher baseline frequencies of NK cells. Peg-IFNalpha treatment was associated with a redistribution of NK cell subsets with increased numbers of CD56bright NK cells whereas total and CD56dim NK cells decreased. During treatment the most mature CD56dim NK cell subsets disappeared from the periphery and the frequency of immature CD56dim NK cells increased. Furthermore, the treatment resulted in decreased multi-functional NK cell responses against K562 cells, with and without additional IFNα stimulation. Taken together, we show that HDV infection increases the amount of NK cells. Furthermore our data suggest a reshaping of the NK pool by IFNα during treatment resulting in a loss of mature cells and decreased functional responses.

Natural killer T cells mediate alveolar bone resorption and a systemic inflammatory response in response to oral infection of mice with Porphyromonas gingivalis

T and B cells are known to be involved in the disease process of periodontitis. However, the role of natural killer T cells in the pathogenesis of periodontitis has not been clarified. To examine the role of these cells, C57BL/6J (wild-type), CD1d(-/-) and α-galactosylceramide (αGC)-stimulated wild-type mice were orally infected with Porphyromonas gingivalis strain W83. Apart from CD1d(-/-) mice, the level of alveolar bone resorption was elevated by the infection and was further accelerated in αGC-stimulated mice. The infection induced elevated levels of serum amyloid A and P.gingivalis-specific IgG in the sera, although the degree of elevation was much smaller in the CD1d(-/-) mice. Infection-induced RANKL elevation was only observed in αGC-stimulated mice. Although the cytokines produced by splenocytes were mainly T-helper 1 type in wild-type mice, those in αGC-stimulated mice were predominantly T-helper 2 type. In the liver, the infection demonstrated no effect on the gene expression for interferon-γ, interleukin-4 and RANKL except αGC-stimulated mice in which the infection upregulated the gene expressions. This study is the first to show that natural killer T cells upregulated systemic and local inflammatory responses induced by oral infection with P.gingivalis, thereby contributing to the progression of alveolar bone resorption.

1021-LB

Aim IL28B and KIR genes with their HLA-C groups ligands were investigated as candidates for persistent HCV infection or HCV clearance in a sample of Rio de Janeiro (Brazil) population. Methods The (rSSO-PCR) was employed to identify KIR genes and pseudogenes and HLA alleles in 181 chronic hepatitis C (CHC) patients, 45 spontaneously recovered (SR), and 214 blood donor healthy individuals (BD). Also, IL28B single nucleotide polymorphisms (SNPs) rs12979860, rs12980275 and rs8099917 were typed by real-time PCR in all groups (CHC = 217 individuals; SR = 45; BD = 191). Results The carrier frequency of KIR2DL2 is higher in SR (73.3%) compared to CHC (55.6%; p = 0.005) and BD (48.9%; p = 0.04) and KIR2DL5 is lower in CHC (46.8%) vs BD (63.3%; p = 0.002). KIR3DS1 was decreased in CHC (24.2%) than SR (46.7%; p = 0.005) and BD (38.3%; p = 0.005). The frequencies of KIR genes and their HLA-C group ligands were significantly different among CHC vs. SR (KIR2DL2/3+C1, p Conclusions We confirmed that KIR2DL2 and KIR3DS1 are associated in resolution of Hepatitis C virus infection and KIR2DL5 with chronic hepatitis. The imbalance between activating and inhibitory KIR and HLA ligands may explain, at least in part, the pathogenesis of the HCV infection. IL28B rs12979860 CC and rs12980275 AA genotype strongly enhances spontaneously resolution of HCV infection. These findings support a role for natural killer (NK) cell activation in clearance of HCV, partially mediated by IL28B among individuals of Rio de Janeiro (Brazil) population.

The role of natural killer T cells in B cell malignancies

Little is known regarding the precise role of different subsets of natural killer T (NKT) cells in the immunopathogenesis of cancer diseases, particularly hematopoietic malignancies. Although it is well known that NKT cells counteract tumor immunity, conflicting reports on the role of NKT cells in hematopoietic malignancies support more investigations to clarify the interactions between NKT cells and the tumor. Among the hematopoietic malignancies, B cell malignancies derive from different stages of B cell maturation in which T cells play a pivotal role. There is evidence which implies the protective role of some subsets of NKT cells in solid cancers as well as B cell malignancies. In this review, we will discuss recent advances about the immunobiology of NKT cells and their precise role in the immunopathogenesis and treatment of different B cell malignancies.

Suppression of NK cells and regulatory T lymphocytes in cats naturally infected with feline infectious peritonitis virus

A strong cell-mediated immunity (CMI) is thought to be indispensable for protection against infection with feline infectious peritonitis virus (FIPV) in cats. In this study, the role of natural killer (NK) cells and regulatory T cells (Tregs), central players in the innate and adaptive CMI respectively, was examined during natural FIPV infection. When quantified, both NK cells and Tregs were drastically depleted from the peripheral blood, mesenteric lymph node (LN) and spleen in FIP cats. In contrast, mesentery and kidney from FIP cats did not show any difference when compared to healthy non-infected control animals. In addition, other regulatory lymphocytes (CD4+CD25−Foxp3+ and CD3+CD8+Foxp3+) were found to be depleted from blood and LN as well. Phenotypic analysis of blood-derived NK cells in FIP cats revealed an upregulation of activation markers (CD16 and CD25) and migration markers (CD11b and CD62L) while LN-derived NK cells showed upregulation of only CD16 and CD62L. LN-derived NK cells from FIPV-infected cats were also significantly less cytotoxic when compared with healthy cats. This study reveals for the first time that FIPV infection is associated with severe suppression of NK cells and Tregs, which is reflected by cell depletion and lowered cell functionality (only NK cells). This will un-doubtfully lead to a reduced capacity of the innate immune system (NK cells) to battle FIPV infection and a decreased capacity (Tregs) to suppress the immunopathology typical for FIP. However, these results will also open possibilities for new therapies targeting specifically NK cells and Tregs to enhance their numbers and/or functionality during FIPV infection.

Analysis of NK cell subsets in children with atopic dermatitis

Event Abstract Back to Event Analysis of NK cell subsets in children with atopic dermatitis Gunnur Deniz1*, Esin Aktas Cetin1, Nilgun Akdeniz1, Safa Baris2, Muhammed Kosker3, Yildiz Camcioglu3 and Isil Barlan2 1 Istanbul University, The Institute of Experimental Medicine (DETAE), Department of Immunology, Turkey 2 Marmara University Medical Faculty, Division of Pediatric Allergy and Immunology, Turkey 3 Istanbul University, Cerrahpasa Faculty of Medicine, Department of Pediatric Infections Disease, Turkey Atopic dermatitis (AD) is a frequent chronic inflammatory skin disease which is often complicated by recurrent microbial superinfections. Numerous studies demonstrated increased frequency of allergen-specific Th2 cells producing increased IL-4, IL-5 and IL-13 in the peripheral blood of AD patients, however little is known about the role of natural killer (NK) cells. In this study, NK1, NK2 and NK regulatory cytokine profiles, the expression of activatory receptors as well as the cytotoxic activity of NK cells in AD were investigated. The study group consists of children with AD (n=14, mean age=7 ± 3.8) and healthy subjects (n=14, mean age=10 ± 4). The patients were multisensitized to at least three aeroallergens and had high serum total IgE levels. Cytotoxic activity, expression of CD16brightCD56dim and CD16dimCD56bright NK cell subsets, NK cell activatory receptors and intracellular IL-4, IL-10 and IFN-g levels were determined by flow cytometry. In AD patients the percentages of CD3-CD16+CD56+, CD16brightCD56dim NK cell subsets and expression of activatory receptors of NKG2D cells were significantly decreased compared to healthy subjects (p=0.000, p=0.000 and p=0.04, respectively). Although, IL-10 secreting regulatory and IL-4 secreting NK2 cells were increased, IFN-g secreting NK1 cells and cytotoxic activity of NK cells were found to be decreased in AD patients (p=0.000, p=0.000, p=0.014 and p=0.016, respectively). Our results suggested that impaired NK cell functions such as decreased expression of CD16bright subset, NKG2D expression as well as cytotoxic activity, high secretion of IL-10 and IL-4 might play a role in the pathogenesis of AD. Keywords: Natural Killer cells, Allergy and Immunology, Cytokines, Cytotoxicity, NAtural Killer Cell subsets Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Innate immunity Citation: Deniz G, Aktas Cetin E, Akdeniz N, Baris S, Kosker M, Camcioglu Y and Barlan I (2013). Analysis of NK cell subsets in children with atopic dermatitis. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00420 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 12 Apr 2013; Published Online: 22 Aug 2013. * Correspondence: Prof. Gunnur Deniz, Istanbul University, The Institute of Experimental Medicine (DETAE), Department of Immunology, Istanbul, Turkey, gdeniz@istanbul.edu.tr Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Gunnur Deniz Esin Aktas Cetin Nilgun Akdeniz Safa Baris Muhammed Kosker Yildiz Camcioglu Isil Barlan Google Gunnur Deniz Esin Aktas Cetin Nilgun Akdeniz Safa Baris Muhammed Kosker Yildiz Camcioglu Isil Barlan Google Scholar Gunnur Deniz Esin Aktas Cetin Nilgun Akdeniz Safa Baris Muhammed Kosker Yildiz Camcioglu Isil Barlan PubMed Gunnur Deniz Esin Aktas Cetin Nilgun Akdeniz Safa Baris Muhammed Kosker Yildiz Camcioglu Isil Barlan Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Increase of Reactive Oxygen Species in Natural Killer cells from Pulmonary Tuberculosis patients

Event Abstract Back to Event Increase of Reactive Oxygen Species in Natural Killer cells from Pulmonary Tuberculosis patients Diogo Silva1, Mónica Abreu1, Patricia Couceiro2, Margarida F. Teixeira1, Inês Ladeira3, Filipa Viveiros3, Raquel Duarte3, Helena Sá1 and Paulo Rodrigues-Santos1* 1 Faculdade de Medicina da Universidade de Coimbra, Instituto de Imunologia, Portugal 2 Center for Neurosciences and Cell Biology, Laboratory of Immunology and Oncology, Portugal 3 Centro Diagnóstico Pneumológico of Vila Nova de Gaia, Portugal Tuberculosis (TB) remains today a threat for public health and one third of the world population is infected. Although the role of Natural Killer (NK) cells in vivo was never fully understood, their capacity to lyse not only infected macrophages, but also directly M. tuberculosis demonstrates their possible role in the immune response in addition to their regulatory function over other immune cells and their presence inside granulomas. However their number is decreased and with impaired function in TB patients Reactive oxygen spices (ROS) produced by tissue-specific cells especially alveolar macrophages can be responsible for their suppressive state as happens in other diseases. In this work we intended to demonstrate the increase of ROS in NK cells of patients with pulmonary tuberculosis. We analyzed by flow cytometry the levels of oxidative stress in cells from peripheral blood of 14 TB patients with main focus in NK cells. In our work we demonstrated that not only phagocytic cells with active NADPH oxidase have an increase of ROS, but also NK cells and NKT cells. We did not find any significant statistical difference in CD8+ T cells comparing with healthy controls. Beyond expected decrease of total NK cell number and especially CD56dim CD16+ subset, we found that almost CD56dim are CD16- corresponding these cells to an increase of oxidative stress. We also demonstrated that contrary to granulocytes and monocytes, in multi-drug resistant (MDR) TB patients the levels of oxidative stress in NK cells are equally higher to persistent TB without (MDR-TB). Keywords: Tuberculosis, Pulmonary, Natural Killer cells, Reactive Oxygen Species, NADPH Oxidase, innate immunity Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Innate immunity Citation: Silva D, Abreu M, Couceiro P, Teixeira MF, Ladeira I, Viveiros F, Duarte R, Sá H and Rodrigues-Santos P (2013). Increase of Reactive Oxygen Species in Natural Killer cells from Pulmonary Tuberculosis patients. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00533 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 11 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Paulo Rodrigues-Santos, Faculdade de Medicina da Universidade de Coimbra, Instituto de Imunologia, Coimbra, 3004-504, Portugal, paulo.santos@fmed.uc.pt Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Diogo Silva Mónica Abreu Patricia Couceiro Margarida F Teixeira Inês Ladeira Filipa Viveiros Raquel Duarte Helena Sá Paulo Rodrigues-Santos Google Diogo Silva Mónica Abreu Patricia Couceiro Margarida F Teixeira Inês Ladeira Filipa Viveiros Raquel Duarte Helena Sá Paulo Rodrigues-Santos Google Scholar Diogo Silva Mónica Abreu Patricia Couceiro Margarida F Teixeira Inês Ladeira Filipa Viveiros Raquel Duarte Helena Sá Paulo Rodrigues-Santos PubMed Diogo Silva Mónica Abreu Patricia Couceiro Margarida F Teixeira Inês Ladeira Filipa Viveiros Raquel Duarte Helena Sá Paulo Rodrigues-Santos Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Role of natural killer (NK) cells during pregnancy: A review

The homeostasis is maintained by the immune system which is constituted a network of organs, cells and molecules that act to combating the assaults affecting the body. The immune function has been conceptually divided into innate immunity and acquired immunity. Among the effector cells of innate immunity are the natural killer cells (NK), they play an important role in the reproductive immunology in the establishment and maintenance of pregnancy and fetus. The study of the biological mechanisms involved in the maintenance of pregnancy contributes to increase knowledge about immune tolerance. The way in which the immune system is modulated, and the study of the recognition systems maternal innate and adaptive occurring during pregnancy, allow to understand the survival of the fetus. The aim of this review was to present the main functions of NK cells and describe their role in the process of trophoblastic invasion in the deployment process, in the maternal-fetal interaction and development of the fetus. The knowledge of the precise role of NK cells is necessary, because these cells may be responsible for reactions which lead to embryonic and fetal loss during the organogenesis process.