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https://www.readbyqxmd.com/read/29679490/increased-nk-cell-subsets-with-inhibitory-cytokines-and-inhibitory-surface-receptors-in-patients-with-recurrent-miscarriage-and-decreased-or-normal-subsets-in-kidney-transplant-recipients-late-post-transplant
#1
Li Zhu, Mostafa Aly, Haihao Wang, Hristos Karakizlis, Rolf Weimer, Christian Morath, Ruben Jeremias Kuon, Bettina Toth, Naruemol Ekpoom, Gerhard Opelz, Volker Daniel
BACKGROUND: Patients with recurrent miscarriage (RM) show up-regulated cytotoxic NK cells that are suspected to play a causal role in abortion. In the present study, we investigated counter-regulating inhibitory mechanisms and compared the results in RM patients with those of healthy controls (HC), patients with end stage renal disease (ESRD) and kidney transplant recipients late post-transplant (TX). METHODS: NK, NKT and T cell subsets were analyzed in the peripheral blood of 31 RM, 14 female ESRD and 9 female TX patients as well as 21 female HC using eight-color fluorescence flow cytometry...
April 21, 2018: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29656052/autologous-serum-collected-1h-post-exercise-enhances-natural-killer-cell-cytotoxicity
#2
Priti Gupta, Austin B Bigley, Melissa Markofski, Mitzi Laughlin, Emily C LaVoy
Natural Killer cells are cytotoxic lymphocytes that recognize and eliminate tumor cells. Exercise enhances NK cell cytotoxic activity (NKCA), yet the underlying mechanisms are not fully understood. Exercise-induced shifts in NK-cell subsets has been proposed as one mechanism. Alternatively, exercise alters stress hormone and cytokine levels, which are also known to affect NKCA. AIM: Determine the role(s) of exercise-induced shifts in the proportions of NK-cell subsets found in the blood, and changes in serum IL-2, IL-6, IL-12, IFN-γ, TNF-α and cortisol, on exercise-induced changes in NKCA...
April 12, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29625837/hbsag-stimulates-nkg2d-receptor-expression-on-natural-killer-cells-and-inhibits-hepatitis-c-virus-replication
#3
Xiao-Xiao Wang, Xiao-Ben Pan, Jin-Chao Han, Xu Cong, Qian Jin, Xiang-Sha Kong, Lai Wei, Bo Feng
BACKGROUND: Higher hepatitis B surface antigen (HBsAg) facilitates hepatitis C virus (HCV) clearance in patients with hepatitis B virus (HBV)/HCV co-infection. We investigated the effect of exogenous HBsAg on the inhibition of HCV replication mediated by natural killer (NK) cells. METHODS: After isolated from peripheral blood of 42 chronic hepatitis B (CHB) patients and 16 healthy individuals, NK cells were co-cultured with HCV-infected Huh7 cells, respectively, with or without HBsAg...
March 26, 2018: Hepatobiliary & Pancreatic Diseases International: HBPD INT
https://www.readbyqxmd.com/read/29616021/adaptive-reconfiguration-of-natural-killer-cells-in-hiv-1-infection
#4
Dimitra Peppa, Isabela Pedroza-Pacheco, Pierre Pellegrino, Ian Williams, Mala K Maini, Persephone Borrow
Human cytomegalovirus (HCMV) co-infection is highly prevalent within HIV-1 cohorts and is an important cofactor in driving ongoing immune activation, even during effective antiretroviral treatment. HCMV infection has recently been associated with expansion of adaptive-like natural killer (NK) cells, which harbor epigenetic alterations that impact on their cellular function and phenotype. The influence of HCMV co-infection on the considerable heterogeneity among NK cells and their functional responses to different stimuli was assessed in a cohort of HIV-1-infected individuals sampled during different stages of infection, compared with healthy subjects stratified according to HCMV serostatus...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29610856/natural-killer-cell-inhibition-by-hla-e-molecules-on-induced-pluripotent-stem-cell-derived-retinal-pigment-epithelial-cells
#5
Sunao Sugita, Kenichi Makabe, Yuko Iwasaki, Shota Fujii, Masayo Takahashi
Purpose: To determine whether human induced pluripotent stem (iPS) cell-derived retinal pigment epithelial (RPE) cells (iPS-RPE) can suppress natural killer (NK) cell activation. Methods: iPS-RPE cells were cocultured with peripheral blood mononuclear cells (PBMCs) or purified NK cells from healthy donors after stimulation with cytokines. To confirm expression of NK cell-specific markers, flow cytometry and quantitative RT-PCR (qRT-PCR) were performed. NK cells (or PBMCs) cocultured with iPS-RPE cells were assessed for proliferation by Ki-67 expression with flow cytometry, and NK suppression by RPE cells was assessed for granzyme B production with ELISA...
April 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29545803/nkg2h-expressing-t-cells-negatively-regulate-immune-responses
#6
Daniela Dukovska, Daniel Fernández-Soto, Mar Valés-Gómez, Hugh T Reyburn
The biology and function of NKG2H receptor, unlike the better characterized members of the NKG2 family NKG2A, NKG2C, and NKG2D, remains largely unclear. Here, we show that NKG2H is able to associate with the signaling adapter molecules DAP12 and DAP10 suggesting that this receptor can signal for cell activation. Using a recently described NKG2H-specific monoclonal antibody (mAb), we have characterized the expression and function of lymphocytes that express this receptor. NKG2H is expressed at the cell surface of a small percentage of peripheral blood mononuclear cell (PBMC) and is found more frequently on T cells, rather than NK cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29536572/multiple-genetically-modified-gtko-hcd46-hla-e-h%C3%AE-2-mg-porcine-hearts-are-protected-from-complement-activation-and-natural-killer-cell-infiltration-during-ex-vivo-perfusion-with-human-blood
#7
Jan-Michael Abicht, Riccardo Sfriso, Bruno Reichart, Matthias Längin, Katja Gahle, Gisella L Puga Yung, Jörg D Seebach, Robert Rieben, David Ayares, Eckhard Wolf, Nikolai Klymiuk, Andrea Baehr, Alexander Kind, Tanja Mayr, Andreas Bauer
BACKGROUND: In pig-to-human xenotransplantation, early cellular rejection reactions are mediated by natural killer cells (NK cells). Human NK cells are inhibited by HLA-E via CD94/NKG2A receptors. To protect porcine grafts against human NK cell responses, transgenic GTKO pigs expressing hCD46 and HLA-E have been generated. The aim of this study was to test the effect of this genetic modification on xenogeneic, and in particular human NK cell response, using an ex vivo perfusion model of pig hearts with human blood...
March 14, 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29514913/contribution-of-nk-cell-education-to-both-direct-and-anti-hiv-1-antibody-dependent-nk-cell-functions
#8
Anne B Kristensen, Stephen J Kent, Matthew S Parsons
Antibody Fc-dependent functions are linked to prevention and control of HIV-1 infection. Basic NK cell biology is likely key to understanding the contributions anti-HIV-1 antibody-dependent NK cell activation and cytolysis make to HIV-1 susceptibility and disease progression. The importance of NK cell education through inhibitory receptors specific for self-HLA-I in determining the potency of anti-HIV-1 antibody mediated NK cell activation and cytolysis is controversial. To address this issue more definitively we utilized HLA-I genotyping, flow cytometry staining panels and cytolysis assays to assess the functionality of educated and non-educated peripheral blood NK cells...
March 7, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29500635/daratumumab-augments-alloreactive-natural-killer-cell-cytotoxicity-towards-cd38-multiple-myeloma-cell-lines-in-a-biochemical-context-mimicking-tumour-microenvironment-conditions
#9
Niken M Mahaweni, Gerard M J Bos, Constantine S Mitsiades, Marcel G J Tilanus, Lotte Wieten
Natural killer (NK) cell-based immunotherapy is a promising novel approach to treat cancer. However, NK cell function has been shown to be potentially diminished by factors common in the tumor microenvironment (TME). In this study, we assessed the synergistic potential of antibody-dependent cell-mediated cytotoxicity (ADCC) and killer immunoglobin-like receptor (KIR)-ligand mismatched NK cells to potentiate NK cell antitumor reactivity in multiple myeloma (MM). Hypoxia, lactate, prostaglandin E2 (PGE2) or combinations were selected to mimic the TME...
March 2, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29491007/fucosyltransferase-induction-during-influenza-virus-infection-is-required-for-the-generation-of-functional-memory-cd4-t-cells
#10
Roberto Tinoco, Florent Carrette, Monique L Henriquez, Yu Fujita, Linda M Bradley
T cells mediating influenza viral control are instructed in lymphoid and nonlymphoid tissues to differentiate into memory T cells that confer protective immunity. The mechanisms by which influenza virus-specific memory CD4+ T cells arise have been attributed to changes in transcription factors, cytokines and cytokine receptors, and metabolic programming. The molecules involved in these biosynthetic pathways, including proteins and lipids, are modified to varying degrees of glycosylation, fucosylation, sialation, and sulfation, which can alter their function...
February 28, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29459477/intrinsic-functional-potential-of-nk-cell-subsets-constrains-retargeting-driven-by-chimeric-antigen-receptors
#11
Vincent Yi Sheng Oei, Marta Siernicka, Agnieszka Graczyk-Jarzynka, Hanna Julie Hoel, Weiwen Yang, Daniel Palacios, Hilde Almåsbak, Malgorzata Bajor, Dennis Clement, Ludwig Brandt, Björn Önfelt, Jodie Goodridge, Magdalena Winiarska, Radoslaw Zagozdzon, Johanna Olweus, Jon-Amund Kyte, Karl-Johan Malmberg
Natural killer (NK) cells hold potential as a source of allogeneic cytotoxic effector cells for chimeric antigen receptor (CAR)-mediated therapies. Here, we explored the feasibility of transfecting CAR-encoding mRNA into primary NK cells and investigated how the intrinsic potential of discrete NK-cell subsets affects retargeting efficiency. After screening five second- and third-generation anti-CD19 CAR constructs with different signaling domains and spacer regions, a third-generation CAR with the CH2-domain removed was selected based on its expression and functional profiles...
February 19, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29447367/endometrial-natural-killer-nk-cells-reveal-a-tissue-specific-receptor-repertoire
#12
D Feyaerts, T Kuret, B van Cranenbroek, S van der Zeeuw-Hingrez, O W H van der Heijden, A van der Meer, I Joosten, R G van der Molen
STUDY QUESTION: Is the natural killer (NK) cell receptor repertoire of endometrial NK (eNK) cells tissue-specific? SUMMARY ANSWER: The NK cell receptor (NKR) expression profile in pre-pregnancy endometrium appears to have a unique tissue-specific phenotype, different from that found in NK cells in peripheral blood, suggesting that these cells are finely tuned towards the reception of an allogeneic fetus. WHAT IS KNOWN ALREADY: NK cells are important for successful pregnancy...
February 13, 2018: Human Reproduction
https://www.readbyqxmd.com/read/29422902/t-cells-engaging-the-conserved-mhc-class-ib-molecule-qa-1b-with-tap-independent-peptides-are-semi-invariant-lymphocytes
#13
Elien M Doorduijn, Marjolein Sluijter, Bianca J Querido, Ursula J E Seidel, Claudia C Oliveira, Sjoerd H van der Burg, Thorbald van Hall
The HLA-E homolog in the mouse (Qa-1b) is a conserved MHC class Ib molecule presenting monomorphic peptides to germline-encoded natural killer receptor CD94/NKG2A. Previously, we demonstrated the replacement of this canonical peptide by a diverse peptidome upon deficiency of the TAP peptide transporter. Analysis of this Qa-1b-restricted T cell repertoire against these non-mutated neoantigens revealed characteristics of conventional hypervariable CD8+ T cells, but also of invariant T cell receptor (TCR)αβ T cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29394121/genetics-of-natural-killer-cells-in-human-health-disease-and-survival
#14
Peter Parham, Lisbeth A Guethlein
Natural killer (NK) cells have vital functions in human immunity and reproduction. In the innate and adaptive immune responses to infection, particularly by viruses, NK cells respond by secreting inflammatory cytokines and killing infected cells. In reproduction, NK cells are critical for genesis of the placenta, the organ that controls the supply of oxygen and nutrients to the growing fetus. Controlling NK cell functions are interactions of HLA class I with inhibitory NK cell receptors. First evolved was the conserved interaction of HLA-E with CD94:NKG2A; later established were diverse interactions of HLA-A, -B, and -C with killer cell immunoglobulin-like receptors...
February 2, 2018: Annual Review of Immunology
https://www.readbyqxmd.com/read/29302013/elevated-hla-a-expression-impairs-hiv-control-through-inhibition-of-nkg2a-expressing-cells
#15
Veron Ramsuran, Vivek Naranbhai, Amir Horowitz, Ying Qi, Maureen P Martin, Yuko Yuki, Xiaojiang Gao, Victoria Walker-Sperling, Gregory Q Del Prete, Douglas K Schneider, Jeffrey D Lifson, Jacques Fellay, Steven G Deeks, Jeffrey N Martin, James J Goedert, Steven M Wolinsky, Nelson L Michael, Gregory D Kirk, Susan Buchbinder, David Haas, Thumbi Ndung'u, Philip Goulder, Peter Parham, Bruce D Walker, Jonathan M Carlson, Mary Carrington
The highly polymorphic human leukocyte antigen ( HLA ) locus encodes cell surface proteins that are critical for immunity. HLA-A expression levels vary in an allele-dependent manner, diversifying allele-specific effects beyond peptide-binding preference. Analysis of 9763 HIV-infected individuals from 21 cohorts shows that higher HLA-A levels confer poorer control of HIV. Elevated HLA-A expression provides enhanced levels of an HLA-A-derived signal peptide that specifically binds and determines expression levels of HLA-E, the ligand for the inhibitory NKG2A natural killer (NK) cell receptor...
January 5, 2018: Science
https://www.readbyqxmd.com/read/29296921/interleukins-12-and-15-induce-cytotoxicity-and-early-nk-cell-differentiation-in-type-3-innate-lymphoid-cells
#16
Ana Raykova, Paolo Carrega, Frank M Lehmann, Robert Ivanek, Vanessa Landtwing, Isaak Quast, Jan D Lünemann, Daniela Finke, Guido Ferlazzo, Obinna Chijioke, Christian Münz
Type 3 innate lymphoid cells (ILC3s) fulfill protective functions at mucosal surfaces via cytokine production. Although their plasticity to become ILC1s, the innate counterparts of type 1 helper T cells, has been described previously, we report that they can differentiate into cytotoxic lymphocytes with many characteristics of early differentiated natural killer (NK) cells. This transition is promoted by the proinflammatory cytokines interleukin 12 (IL-12) and IL-15, and correlates with expression of the master transcription factor of cytotoxicity, eomesodermin (Eomes)...
December 26, 2017: Blood Advances
https://www.readbyqxmd.com/read/29247515/intrahepatic-and-peripheral-blood-phenotypes-of-natural-killer-and-t-cells-differential-surface-expression-of-killer-cell-immunoglobulin-like-receptors
#17
Ariel Podhorzer, Andrés Machicote, Santiago Belén, Leandro Lauferman, Oscar Imventarza, Silvina Montal, Sebastián Marciano, Omar Galdame, Luis G Podesta, Leonardo Fainboim
Deep characterization of the frequencies, phenotypes and functionalities of liver and peripheral blood natural killer (NK), natural killer T (NKT) and T cells from healthy individuals is an essential step to further interpret changes in liver diseases. These data indicate that CCR7, a chemokine essential for cell migration through lymphoid organs, is almost absent in liver NK and T cells. CD56bright NK cells, which represent half of liver NK cells, showed lower expression of the inhibitory molecule NKG2A and an increased frequency of the activation marker NKp44...
December 16, 2017: Immunology
https://www.readbyqxmd.com/read/29209315/gradual-increase-of-fc%C3%AE-riiia-cd16a-expression-and-shift-toward-ifn-%C3%AE-secretion-during-differentiation-of-cd56-dim-natural-killer-cells
#18
Laurie Lajoie, Nicolas Congy-Jolivet, Armelle Bolzec, Gilles Thibault
Natural killer (NK) cell effector functions include cytotoxicity and secretion of cytokines such as interferon-γ (IFN-γ). The immature CD56bright subset of human NK cells lacks expression of FcγRIIIa/CD16a, one of the low-affinity immunoglobulin G receptors, or exhibits low-density expression (CD56bright CD16-/dim ) and produces IFN-γ in response to cytokine stimulation, whereas the mature CD56dim CD16+ subset is the most cytotoxic one. A further differentiation/maturation of the latter subset according to the gradual loss of NKG2A and/or gain of KIR2DL (CD158a and CD158b) has been demonstrated and the ability to produce IFN-γ in response to activating receptor (AR) co-engagement is gradually acquired during terminal differentiation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29186689/lymphocytes-negatively-regulate-nk-cell-activity-via-qa-1b-following-viral-infection
#19
Haifeng C Xu, Jun Huang, Aleksandra A Pandyra, Elisabeth Lang, Yuan Zhuang, Christine Thöns, Jörg Timm, Dieter Häussinger, Marco Colonna, Harvey Cantor, Karl S Lang, Philipp A Lang
NK cells can reduce anti-viral T cell immunity during chronic viral infections, including infection with the lymphocytic choriomeningitis virus (LCMV). However, regulating factors that maintain the equilibrium between productive T cell and NK cell immunity are poorly understood. Here, we show that a large viral load resulted in inhibition of NK cell activation, which correlated with increased expression of Qa-1b, a ligand for inhibitory NK cell receptors. Qa-1b was predominantly upregulated on B cells following LCMV infection, and this upregulation was dependent on type I interferons...
November 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/29182664/differential-inhibitory-and-activating-nk-cell-receptor-levels-and-nk-nkt-like-cell-functionality-in-chronic-and-recovered-stages-of-chikungunya
#20
Subrat Thanapati, Mohini A Ganu, Anuradha S Tripathy
The role of natural killer (NK; CD3-CD56+)/NKT (CD3+CD56+)-like cells in chikungunya virus (CHIKV) disease progression/recovery remains unclear. Here, we investigated the expression profiles and function of NK and NKT-like cells from 35 chronic chikungunya patients, 30 recovered individuals, and 69 controls. Percentage of NKT-like cells was low in chronic chikungunya patients. NKp30+, CD244+, DNAM-1+, and NKG2D+ NK cell percentages were also lower (MFI and/or percentage), while those of CD94+ and NKG2A+ NKT-like cells were higher (MFI and/or percentage) in chronic patients than in recovered subjects...
2017: PloS One
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