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https://www.readbyqxmd.com/read/28335588/recovery-of-nk-cd56-cd3-cells-after-1-year-of-tenofovir-therapy-for-chronic-hepatitis-b-infection
#1
Hwan Hee Lee, Hyojeung Kang, Hyosun Cho
Natural killer (NK) cells have been reported to be dysfunctional in chronic hepatitis B (CHB) infection. However, the functional recovery of NK cells was not clearly understood under anti-viral therapeutic agents in CHB. In this study, we investigated the phenotypic changes of NK(CD56+CD3-) cells in terms of their functional markers (CD16, NKG2A, NKG2D) during tenofovir therapy in CHB. The frequency of NK(CD56+CD3-) cells in CHB patients was significantly increased after 12 months of tenofovir therapy when compared to baseline...
March 24, 2017: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28322797/transcriptional-activation-of-the-mica-gene-with-an-engineered-crispr-cas9-system
#2
Kazuma Sekiba, Mari Yamagami, Motoyuki Otsuka, Tatsunori Suzuki, Takahiro Kishikawa, Rei Ishibashi, Motoko Ohno, Masaya Sato, Kazuhiko Koike
Major histocompatibility complex class I polypeptide-related sequence A (MICA) is a prototypical NKG2D ligand. Because immune cells, such as natural killer (NK) cells, recognize virally infected or transformed cells and eliminate them through the interaction between NKG2D receptors on NK cells and NKG2D ligands on pathogenic cells, MICA expression levels are associated with NK cell-mediated immunity. Here, we report that an engineered clustered regularly interspaced short palindromic repeats-Cas9-related complex targeting MICA gene promoter sequences activates transcription of the MICA gene from its endogenous locus...
March 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28318408/bone-marrow-derived-mesenchymal-stem-cells-attenuate-immune-mediated-liver-injury-and-compromise-virus-control-during-acute-hepatitis-b-virus-infection-in-mice
#3
Mengmeng Qu, Xu Yuan, Dan Liu, Yuhong Ma, Jun Zhu, Jun Cui, Mengxue Yu, Changyong Li, Deyin Guo
Mesenchymal stem cells (MSCs) have been used as therapeutic tools not only for their ability to differentiate toward different cells, but also for their unique immunomodulatory properties. However, it is still unknown how MSCs may affect immunity during hepatitis B virus (HBV) infection. This study was designed to explore the effect of bone marrow-derived MSCs (BM-MSCs) on hepatic natural killer (NK) cells in a mouse model of acute HBV infection. Mice were injected with 1 × 10(6) BM-MSCs, which stained with chloromethyl derivatives of fluorescein diacetate fluorescent probe, 24 h before hydrodynamic injection of viral DNA (pHBV1...
February 2, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28295190/phase-i-study-of-cord-blood-derived-natural-killer-cells-combined-with-autologous-stem-cell-transplantation-in-multiple-myeloma
#4
Nina Shah, Li Li, Jessica McCarty, Indreshpal Kaur, Eric Yvon, Hila Shaim, Muharrem Muftuoglu, Enli Liu, Robert Z Orlowski, Laurence Cooper, Dean Lee, Simrit Parmar, Kai Cao, Catherine Sobieiski, Rima Saliba, Chitra Hosing, Sairah Ahmed, Yago Nieto, Qaiser Bashir, Krina Patel, Catherine Bollard, Muzaffar Qazilbash, Richard Champlin, Katy Rezvani, Elizabeth J Shpall
Multiple myeloma (MM) is a disease with known immune dysregulation. Natural killer (NK) cells have shown preclinical activity in MM. We conducted a first-in-human study of umbilical cord blood-derived (CB) NK cells for MM patients undergoing high dose chemotherapy and autologous haematopoietic stem cell transplantation (auto-HCT). Patients received lenalidomide (10 mg) on days -8 to -2, melphalan 200 mg/m(2) on day -7, CB-NK cells on day -5 and auto-HCT on day 0. Twelve patients were enrolled, three on each of four CB-NK cell dose levels: 5 × 10(6) , 1 × 10(7) , 5 × 10(7) and 1 × 10(8) CB-NK cells/kg...
March 14, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28294381/cd3-cd8-nkg2d-t-lymphocytes-induce-apoptosis-and-necroptosis-in-hla-negative-cells-via-fasl-fas-interaction
#5
O K Ivanova, T N Sharapova, E A Romanova, L P Sashchenko, D V Yashin
An important problem in cellular immunology is to identify new populations of cytotoxic lymphocytes capable of killing tumor cells that have lost classical components of MHC-machinery and to understand mechanisms of the death of these cells. We have previously found that CD4(+) CD25(+) lymphocytes appear in the lymphokine-activated killer (LAK) cell culture, which carry Tag7 (PGRP-S) and FasL proteins on their surface and can kill Hsp70- and Fas-expressing HLA-negative cells. In this work, we have continued to study the mechanisms of killing of the HLA-negative tumor cells, focusing this time on the CD8+ lymphocytes...
March 15, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28293239/major-histocompatibility-complex-class-i-chain-related-a-mica-molecules-relevance-in-solid-organ-transplantation
#6
REVIEW
Ajay Kumar Baranwal, Narinder K Mehra
An ever growing number of reports on graft rejection and/or failure even with good HLA matches have highlighted an important role of non-HLA antigens in influencing allograft immunity. The list of non-HLA antigens that have been implicated in graft rejection in different types of organ transplantation has already grown long. Of these, the Major Histocompatibility Complex class I chain-related molecule A (MICA) is one of the most polymorphic and extensively studied non-HLA antigenic targets especially in the kidney transplantation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28289413/mica-and-nkg2d-is-there-an-impact-on-kidney-transplant-outcome
#7
REVIEW
Matilde Risti, Maria da Graça Bicalho
This paper aims to present an overview of MICA and natural killer group 2 member D (NKG2D) genetic and functional interactions and their impact on kidney transplant outcome. Organ transplantation has gone from what can accurately be called a "clinical experiment" to a routine and reliable practice, which has proven to be clinically relevant, life-saving and cost-effective when compared with non-transplantation management strategies of both chronic and acute end-stage organ failures. The kidney is the most frequently transplanted organ in the world (transplant-observatory)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28283665/il-18-dependent-nkg2d-ligand-upregulation-on-accessory-cells-is-mediated-by-the-pi3k-gsk-3-pathway
#8
Joshua D Brandstadter, Huiyao Chen, Songfu Jiang, Xiaopei Huang, Yiping Yang
NK cells are critical for the control of viral infections. Studies have shown that efficient NK cell activation in response to infection with VV in vivo requires multiple pathways, including the NKG2D pathway. We have recently shown that IL-18 is necessary for the activation of NK cells through upregulation of the NKG2D ligand Rae-1 on DCs upon VV infection. However, how IL-18R signaling on the accessory cells contributes to Rae-1 up-regulation remains to be defined. In this study, we found IL-18-mediated Rae-1 up-regulation in accessory cells, including macrophages and DCs, to be dependent on the MyD88-PI3K pathway...
March 10, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28282548/attenuated-in-vitro-effects-of-ifn-%C3%AE-il-2-and-il-12-on-functional-and-receptor-characteristics-of-peripheral-blood-lymphocytes-in-metastatic-melanoma-patients
#9
Katarina M Mirjačić Martinović, Ana M Vuletić, Nada Lj Babović, Radan R Džodić, Gordana M Konjević, Vladimir B Jurišić
Considering tumor-induced suppression of lymphocytes the aim of this study was to investigate in vitro effects of IFN-α, IL-2, IL-12 and IL-18 as immunomodulating agents on the functional and receptor characteristics of peripheral blood lymphocytes (PBL) in metastatic melanoma (MM) patients compared to healthy controls (HC). In HC IFN-α, IL-2 and IL-12 enhanced mRNA level of perforin by inducing pSTAT-1 and pSTAT-5 signaling molecules. Additionally, the expression of NKG2D activating receptor and its DAP10 signaling molecule was upregulated by IL-2...
March 7, 2017: Cytokine
https://www.readbyqxmd.com/read/28281564/standardized-and-flexible-eight-colour-flow-cytometry-panels-harmonized-between-different-laboratories-to-study-human-nk-cell-phenotype-and-function
#10
John P Veluchamy, María Delso-Vallejo, Nina Kok, Fenna Bohme, Ruth Seggewiss-Bernhardt, Hans J van der Vliet, Tanja D de Gruijl, Volker Huppert, Jan Spanholtz
Advancements in multi-colour fluorescence activated cell sorting (FACS) panel warrant harmonized procedures to obtain comparable data between various laboratories. The intensifying clinical exploration of Natural Killer (NK) cell-based immunotherapy demands standardized and harmonized NK cell FACS panels and acquisition protocols. Eight colour FACS panels were designed to study human NK cell phenotype and function within peripheral blood mononuclear cells (PBMC). The panels were designed around fixed backbone markers and channels, covering antigens for non-NK lineage exclusion (CD3, TCRγδ, CD19, CD14, SYTOX(®) Blue) and NK cell selection (CD45, CD56, CD16), complemented with variable drop-in markers/channels to study NK cell phenotype (NKG2A, NKG2C, NKG2D and KIR2D) or NK cell function and activation (CD25, NKp44 and CD107a)...
March 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28276625/nkg2d-ligand-rae1%C3%AE%C2%B5-induces-generation-and-enhances-the-inhibitor-function-of-myeloid-derived-suppressor-cells-in-mice
#11
Li Qian, Yang Liu, Shaoqing Wang, Weijuan Gong, Xiaoqin Jia, Lu Liu, Feng Ye, Jingjuan Ding, Yuwei Xu, Yi Fu, Fang Tian
Expression of surface NKG2D ligands on tumour cells, which activates nature killer (NK) cells and CD8(+) T cells, is crucial in antitumour immunity. Some types of tumours have evolved mechanisms to suppress NKG2D-mediated immune cell activation, such as tumour-derived soluble NKG2D ligands or sustained NKG2D ligands produced by tumours down-regulate the expression of NKG2D on NK cells and CD8(+) T cells. Here, we report that surface NKG2D ligand RAE1ε on tumour cells induces CD11b(+) Gr-1(+) myeloid-derived suppressor cell (MDSC) via NKG2D in vitro and in vivo...
March 9, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28273905/nkg2d-modulates-aggravation-of-liver-inflammation-by-activating-nk-cells-in-hbv-infection
#12
Yadong Wang, Wei Wang, Chuan Shen, Yong Wang, Mingjing Jiao, Weiyan Yu, Hongzhu Yin, Xiaobo Shang, Qianfei Liang, Caiyan Zhao
Hepatitis B virus (HBV) infection is thought to be an immune-mediated liver disease. The mechanisms underlying natural killer (NK) cell group 2D receptor (NKG2D) that activates NK cells and participates in anti-HBV immunity and immunopathology has not been thoroughly elucidated. Peripheral NKG2D(+) and IFN-γ(+) NK cells frequencies and intrahepatic NKG2D and IFN-γ mRNA and protein expressions were determined in HBV-infected patients. Levels of NKG2D and IFN-γ mRNA and protein in NK cells, co-cultured with HBV-replicating HepG2 cells with or without NKG2D blockade, were analyzed...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28251796/cytotoxicity-of-natural-killer-cells-activated-through-nkg2d-contributes-to-the-development-of-bronchiolitis-obliterans-in-a-murine-heterotopic-tracheal-transplant-model
#13
Toru Kawakami, Koyu Ito, Yasushi Matsuda, Masahumi Noda, Akira Sakurada, Yasushi Hoshikawa, Yoshinori Okada, Kouetsu Ogasawara
Bronchiolitis obliterans after lung transplantation is a major cause of postoperative mortality in which T cell-mediated immunity is known to play an important role. However, the exact contribution of NK cells, which have similar functions to CD8(+) T cells, has not been defined. Here, we assessed the role of NK cells in murine bronchiolitis obliterans through heterotopic tracheal transplantations and found a greater percentage of NK cells in allografts than in isografts. Depletion of NK cells using an anti-NK1...
March 1, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28245380/-decitabine-enhances-the-sensitivity-of-leukemia-stem-cell-to-allo-nk-cell-mediated-killing
#14
Qian Li, Shan-Shan Wei, Jin-Gao Li, Shao-Xian Chen, Jing Chen, Hui-Ting Huang, Qi Peng, Ping-Fang Xia, Miao-Rong She
OBJECTIVE: To investigate the allo-NK cell-mediated killing effect enhanced by decitabine on leukemia stem cells(LSC) and the underlying mechanisms. METHODS: LSC were separated from KG1a cells by using immunomagnetic beads. Allo-NK cells were isolated and purified from PBMC of healthy donors. Cytotoxicity of allo-NK cells against LSC were measured by LDH releasing assay. The apoptosis induced by allo-NK cells in LSC and the expressions of NKG2D ligands including MICA/B and ULBP1-3 on LSC were detected by flow cytometry...
February 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28239678/bidirectional-intragraft-alloreactivity-drives-the-repopulation-of-human-intestinal-allografts-and-correlates-with-clinical-outcome
#15
Julien Zuber, Brittany Shonts, Sai-Ping Lau, Aleksandar Obradovic, Jianing Fu, Suxiao Yang, Marion Lambert, Shana Coley, Joshua Weiner, Joseph Thome, Susan DeWolf, Donna L Farber, Yufeng Shen, Sophie Caillat-Zucman, Govind Bhagat, Adam Griesemer, Mercedes Martinez, Tomoaki Kato, Megan Sykes
A paradigm in transplantation states that graft-infiltrating T cells are largely non-alloreactive "bystander" cells. However, the origin and specificity of allograft T cells over time has not been investigated in detail in animals or humans. Here, we use polychromatic flow cytometry and high throughput TCR sequencing of serial biopsies to show that gut-resident T cell turnover kinetics in human intestinal allografts are correlated with the balance between intra-graft host-vs-graft (HvG) and graft-vs-host (GvH) reactivities and with clinical outcomes...
October 2016: Science Immunology
https://www.readbyqxmd.com/read/28237999/the-poly-%C3%AE-d-glutamic-acid-capsule-surrogate-of-bacillus-anthracis-capsule-induces-interferon-gamma-production-in-nk-cells-through-interactions-with-macrophages
#16
Hae-Ri Lee, Jun Ho Jeon, Gi-Eun Rhie
The poly-γ-D-glutamic acid (PGA) capsule, a major virulence factor of Bacillus anthracis, provides protection of the Bacillus from phagocytosis and allows its unimpeded growth in the host. We investigated crosstalk between murine NK cells and macrophages stimulated with PGA capsule of Bacillus licheniformis, a surrogate of B. anthracis capsule. PGA induced interferon-gamma (IFN-γ) production from NK cells cultured with macrophages. This effect was dependent on macrophage-derived IL-12 and cell-cell contact interaction with macrophages through NK cell receptor NKG2D and its ligand RAE-1...
February 24, 2017: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28236750/targeting-nk-cell-checkpoints-for-cancer-immunotherapy
#17
REVIEW
Aura Muntasell, Maria C Ochoa, Luna Cordeiro, Pedro Berraondo, Ascension López-Díaz de Cerio, Mariona Cabo, Miguel López-Botet, Ignacio Melero
Natural Killer (NK) cells are cytotoxic lymphocytes specialized in early defense against virus-infected and transformed cells. NK-cell function is regulated by activating and inhibitory surface receptors recognizing their ligands on transformed cells. Modulation of NK numbers and/or function by a variety of agents such as cytokines and monoclonal antibodies may result in enhanced anti-tumor activity. Recombinant cytokines (i.e., IL-15 and IL-2), antibodies blocking inhibitory receptors (i.e., KIR, NKG2A and TIGIT) and agonists delivering signals via CD137, NKG2D and CD16 stand out as the most suitable opportunities...
February 22, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28235675/il-15-stimulates-nkg2d-while-promoting-igm-expression-of-b-1a-cells
#18
Amlan Kanti Ghosh, Debolina Sinha, Ratna Biswas, Tapas Biswas
Interleukin (IL)-15, a key manipulator of T-cell function also modulates B-1a cell activity by augmenting activation markers, turning them towards type 1 polarization and immunoglobulin (Ig) expression which is significant in the context of gut immunity. Here we show, for the first time, IL-15 mediated up-regulation of the activation receptor NKG2D and its adaptor DAP10 in B-1a cells indicating their essential coupling with IL-15 receptor signaling pathway. Our results demonstrate IL-15 treatment increases phosphorylation of STAT5 and p38 leading to translocation of NF-κB onto the nucleus, an attribute that delineates activation of B-1a cells and its role in inflammation...
February 21, 2017: Cytokine
https://www.readbyqxmd.com/read/28224733/nk1-1-cd4-nkg2d-t-cells-suppress-dss-induced-colitis-in-mice-through-production-of-tgf-%C3%AE
#19
Xingxing Qian, Chunxia Hu, Sen Han, Zhijie Lin, Weiming Xiao, Yanbing Ding, Yu Zhang, Li Qian, Xiaoqing Jia, Guoqiang Zhu, Weijuan Gong
CD4(+) NKG2D(+) T cells are associated with tumour, infection and autoimmune diseases. Some CD4(+) NKG2D(+) T cells secrete IFN-γ and TNF-α to promote inflammation, but others produce TGF-β and FasL to facilitate tumour evasion. Here, murine CD4(+) NKG2D(+) T cells were further classified into NK1.1(-) CD4(+) NKG2D(+) and NK1.1(+) CD4(+) NKG2D(+) subpopulations. The frequency of NK1.1(-) CD4(+) NKG2D(+) cells decreased in inflamed colons, whereas more NK1.1(+) CD4(+) NKG2D(+) cells infiltrated into colons of mice with DSS-induced colitis...
February 22, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28223394/primary-adrenal-insufficiency-is-associated-with-impaired-natural-killer-cell-function-a-potential-link-to-increased-mortality
#20
Irina Bancos, Jon Hazeldine, Vasileios Chortis, Peter Hampson, Angela E Taylor, Janet M Lord, Wiebke Arlt
OBJECTIVE: Mortality in patients with primary adrenal insufficiency (PAI) is significantly increased, with respiratory infections as a major cause of death. Moreover, patients with PAI report an increased rate of non-fatal infections. Neutrophils and natural killer (NK) cells are innate immune cells that provide frontline protection against invading pathogens. Thus, we compared the function and phenotype of NK cells and neutrophils isolated from PAI patients and healthy controls to ascertain whether altered innate immune responses could be a contributory factor for the increased susceptibility of PAI patients to infection...
April 2017: European Journal of Endocrinology
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