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https://www.readbyqxmd.com/read/28810810/reduced-expression-of-siglec-7-nkg2a-and-cd57-on-terminally-differentiated-cd56-cd16-nk-cell-subset-is-associated-with-nk-cell-dysfunction-in-chronic-hiv-1-clade-c-infection
#1
Michael Zulu, Kewreshini Naidoo, Zenele Mncube, Manjeetha Jaggernath, Philip Jr Goulder, Thumbi Ndung'u, Marcus Altfeld, Christina Fanesa Thobakgale
BACKGROUND: HIV-1 viremia has been shown to induce several phenotypic and functional abnormalities in natural killer (NK) cells. To assess immune defects associated with HIV viremia, we examined NK cell function, differentiation status and phenotypic alterations based on expression of inhibitory and activating receptors on NK cells in HIV-1 subtype C chronically infected participants from Durban, South Africa. METHODS: NK cell phenotypic profiles were characterized by assessing Siglec-7, NKG2A and NKG2C markers on frozen peripheral blood mononuclear cells (PBMCs) from viremic, antiretroviral therapy (ART)-naïve HIV-1 chronically infected participants (n=23), HIV-1 chronically infected participants who have been on combination antiretroviral therapy (cART) for at least 12 months (n=23) compared to healthy donors (n=23)...
August 16, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28783683/class-i-hla-haplotypes-form-two-schools-that-educate-nk-cells-in-different-ways
#2
Amir Horowitz, Zakia Djaoud, Neda Nemat-Gorgani, Jeroen Blokhuis, Hugo G Hilton, Vivien Béziat, Karl-Johan Malmberg, Paul J Norman, Lisbeth A Guethlein, Peter Parham
Natural killer (NK) cells are lymphocytes that have vital functions in innate and adaptive immunity, as well as placental reproduction. Polymorphic human leukocyte antigen (HLA) class I educates NK cells through interactions with killer cell immunoglobulin-like receptors (KIRs) and by supplying peptides that bind HLA-E to form ligands for CD94/NKG2A receptors on NK cells. HLA-B dimorphism in the leader peptide modulates this latter function: -21methionine (-21M) delivers functional peptides, but -21threonine (-21T) does not...
September 9, 2016: Science Immunology
https://www.readbyqxmd.com/read/28769923/natural-killer-cells-from-patients-with-recombinase-activating-gene-and-non-homologous-end-joining-gene-defects-comprise-a-higher-frequency-of-cd56-bright-nkg2a-cells-and-yet-display-increased-degranulation-and-higher-perforin-content
#3
Kerry Dobbs, Giovanna Tabellini, Enrica Calzoni, Ornella Patrizi, Paula Martinez, Silvia Clara Giliani, Daniele Moratto, Waleed Al-Herz, Caterina Cancrini, Morton Cowan, Jacob Bleesing, Claire Booth, David Buchbinder, Siobhan O Burns, Talal A Chatila, Janet Chou, Vanessa Daza-Cajigal, Lisa M Ott de Bruin, MaiteTeresa de la Morena, Gigliola Di Matteo, Andrea Finocchi, Raif Geha, Rakesh K Goyal, Anthony Hayward, Steven Holland, Chiung-Hui Huang, Maria G Kanariou, Alejandra King, Blanka Kaplan, Anastasiya Kleva, Taco W Kuijpers, Bee Wah Lee, Vassilios Lougaris, Michel Massaad, Isabelle Meyts, Megan Morsheimer, Benedicte Neven, Sung-Yun Pai, Alessandro Plebani, Susan Prockop, Ismail Reisli, Jian Yi Soh, Raz Somech, Troy R Torgerson, Yae-Jaen Kim, Jolan E Walter, Andrew R Gennery, Sevgi Keles, John P Manis, Emanuela Marcenaro, Alessandro Moretta, Silvia Parolini, Luigi D Notarangelo
Mutations of the recombinase-activating genes 1 and 2 (RAG1 and RAG2) in humans are associated with a broad range of phenotypes. For patients with severe clinical presentation, hematopoietic stem cell transplantation (HSCT) represents the only curative treatment; however, high rates of graft failure and incomplete immune reconstitution have been observed, especially after unconditioned haploidentical transplantation. Studies in mice have shown that Rag(-/-) natural killer (NK) cells have a mature phenotype, reduced fitness, and increased cytotoxicity...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28747319/frontline-science-a-hyporesponsive-subset-of-rat-nk-cells-negative-for-ly49s3-and-nkr-p1b-are-precursors-to-the-functionally-mature-nkr-p1b-subset
#4
Amanda Sudworth, John T Vaage, Marit Inngjerdingen, Lise Kveberg
Rat NK cells are divided into major subsets expressing either Ly49 receptors or the inhibitory NKR-P1B receptor in conjunction with NKG2A/C/E receptors. A minor subset of NKp46(+) cells lacking expression of both Ly49 receptors and NKR-P1B is present in blood and spleen and is associated with decreased functional competence. We hypothesized that this subset may represent precursors to Ly49(+) and/or NKR-P1B(+) NK cells. When cultured in vitro in IL-2 and IL-15 or adoptively transferred to syngeneic hosts, a portion of NKR-P1B (-) Ly49s3 (-) cells transformed to express NKR-P1B, but very little Ly49s3...
July 26, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28674534/human-cd56-dim-cd16-dim-cells-as-an-individualized-natural-killer-cell-subset
#5
Mathieu Amand, Gilles Iserentant, Aurélie Poli, Marwan Sleiman, Virginie Fievez, Isaura Pilar Sanchez, Nicolas Sauvageot, Tatiana Michel, Nasséra Aouali, Bassam Janji, Claudia Milena Trujillo-Vargas, Carole Seguin-Devaux, Jacques Zimmer
Human natural killer (NK) cells can be subdivided in several subpopulations on the basis of the relative expression of the adhesion molecule CD56 and the activating receptor CD16. Whereas blood CD56(bright)CD16(dim/-) NK cells are classically viewed as immature precursors and cytokine producers, the larger CD56(dim)CD16(bright) subset is considered as the most cytotoxic one. In peripheral blood of healthy donors, we noticed the existence of a population of CD56(dim)CD16(dim) NK cells that was frequently higher in number than the CD56(bright) subsets and even expanded in occasional control donors but also in transporter associated with antigen processing-deficient patients, two familial hemophagocytic lymphohistiocytosis type II patients, and several common variable immunodeficiency patients...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28653491/the-role-of-%C3%AE-%C3%AE-t-cells-during-human-pregnancy
#6
Chunyu Huang, Yong Zeng, Wenwei Tu
Pregnancy is an evolutionarily important and mysterious process. The placenta, as the nutrient and gas exchange organ, plays an essential role during this process. In addition, the interaction between trophoblast and maternal immune cells at the maternal-fetal interface is also associated with successful pregnancy. Human leukocyte antigen (HLA) molecules on trophoblast cells are involved in protecting the fetus from maternal rejection. Trophoblast cells comprise three subpopulations, including syncytiotrophoblast cells, cytotrophoblast cells, and extravillous trophoblast cells, and these cells express different HLA molecules...
June 27, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28641645/-subtype-and-functional-biomarker-changes-of-nk-cells-in-peripheral-blood-of-patients-with-myelodysplastic-syndrome
#7
Shu-Juan Xu, Zong-Hong Shao, Rong Fu, Hua-Quan Wang, Hui Liu, Chun-Yan Liu, Wei Zhang
OBJECTIVE: To analyze the subtype and functional biomarker expression changes of natural kill cells(NK) in peripheral blood of patients with myelodysplastic syndrome(MDS) and normal people, so as to evaluate the relationships between these changes and hematopoietic functions and to explore the role of NK cells in the pathogenesis of MDS. METHODS: The quantity of NK cells and the expression of biomarkers(NKp30,NKp46,NKG2A) on NK cells were detected by flow cytometry in 35 MDS patients from 2015 to 2016 in our hospital and 34 normal controls...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28639033/functional-restoration-of-cd56-bright-nk-cells-facilitates-immune-control-via-il-15-and-nkg2d-in-patients-under-antiviral-treatment-for-chronic-hepatitis-b
#8
Tao Chen, Lin Zhu, Aichao Shi, Lin Ding, Xiaoping Zhang, Zhenmin Tan, Wei Guo, Weiming Yan, Meifang Han, Jidong Jia, Xiaoping Luo, Detlef Schuppan, Qin Ning
BACKGROUND AND AIMS: Hepatitis B virus (HBV) is intrinsically immunogenic, with long-lasting immune control in many patients. However, the mechanisms and key cell types underlying effective immune control are incompletely understood. METHODS: We studied the restoration of natural killer (NK) cell numbers and function post antiviral treatment in 52 hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients who received telbivudine (LdT) for 48 weeks...
June 20, 2017: Hepatology International
https://www.readbyqxmd.com/read/28605050/the-abl-1-kinase-is-dispensable-for-nk-cell-inhibitory-signaling-and-is-not-involved-in-murine-nk-cell-education
#9
S Ganesan, T L Thanh, N Kadri, B J Chambers, S Meinke, P Brodin, E Vivier, D M Wetzel, A J Koleske, P Höglund
Natural killer (NK) cell responsiveness in the mouse is determined in an education process guided by inhibitory Ly49 and NKG2A receptors binding to MHC class I molecules. It has been proposed that inhibitory signaling in human NK cells involves Abl-1 (c-Abl)-mediated phosphorylation of Crk, lowering NK cell function via disruption of a signaling complex including C3G and c-Cbl, suggesting that NK cell education might involve c-Abl. Mice deficient in c-Abl expression specifically in murine NK cells displayed normal inhibitory and activating receptor repertoires...
June 12, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28603523/kir3ds1-mediated-recognition-of-hla-b51-modulation-of-kir3ds1-responsiveness-by-self-hla-b-allotypes-and-effect-on-nk-cell-licensing
#10
Simona Carlomagno, Michela Falco, Maria Bono, Claudia Alicata, Lucia Garbarino, Michela Mazzocco, Lorenzo Moretta, Alessandro Moretta, Simona Sivori
Several studies described an association between killer-cell immunoglobulin-like receptor (KIR)/HLA gene combinations and clinical outcomes in various diseases. In particular, an important combined role for KIR3DS1 and HLA-B Bw4-I80 in controlling viral infections and a higher protection against leukemic relapses in donor equipped with activating KIRs in haplo-HSCT has been described. Here, we show that KIR3DS1 mediates positive signals upon recognition of HLA-B*51 (Bw4-I80) surface molecules on target cells and that this activation occurs only in Bw4-I80(neg) individuals, including those carrying particular KIR/HLA combination settings...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28576831/shifting-the-balance-of-activating-and-inhibitory-natural-killer-receptor-ligands-on-braf-v600e-melanoma-lines-with-vemurafenib
#11
Alexandra Frazao, Marina Colombo, Emmanuelle Fourmentraux-Neves, Meriem Messaoudene, Sylvie Rusakiewicz, Laurence Zitvogel, Eric Vivier, Frederic Vely, Florence Faure, Brigitte Dreno, Houssem Benlalam, Fanny Bouquet, Ariel Savina, Eric Pasmant, Antoine Toubert, Marie Francoise Avril, Anne Caignard
Over 60% of human melanoma tumors bear a mutation in the BRAF gene. The most frequent mutation is a substitution at codon 600 (V600E), leading to a constitutively active BRAF and overactivation of the mitogen-activated protein kinase (MAPK) pathway. Patients harboring mutated BRAF respond to kinase inhibitors such as vemurafenib. However, these responses are transient and relapses are frequent. Melanoma cells are efficiently lysed by activated natural killer (NK) cells. Melanoma cells express several stress-induced ligands that are recognized by activating NK cell receptors...
June 2, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28561023/expression-of-cd226-is-associated-to-but-not-required-for-nk-cell-education
#12
Arnika K Wagner, Nadir Kadri, Johanna Snäll, Petter Brodin, Susan Gilfillan, Marco Colonna, Günter Bernhardt, Petter Höglund, Klas Kärre, Benedict J Chambers
DNAX accessory molecule-1 (DNAM-1, also known as CD226) is an activating receptor expressed on subsets of natural killer (NK) and T cells, interacts with its ligands CD155 or CD112, and has co-varied expression with inhibitory receptors. Since inhibitory receptors control NK-cell activation and are necessary for MHC-I-dependent education, we investigated whether DNAM-1 expression is also involved in NK-cell education. Here we show an MHC-I-dependent correlation between DNAM-1 expression and NK-cell education, and an association between DNAM-1 and NKG2A that occurs even in MHC class I deficient mice...
May 31, 2017: Nature Communications
https://www.readbyqxmd.com/read/28555134/the-transcription-factor-znf683-hobit-regulates-human-nk-cell-development
#13
Mirte Post, Angelica Cuapio, Markus Osl, Dorit Lehmann, Ulrike Resch, David M Davies, Martin Bilban, Bernhard Schlechta, Wolfgang Eppel, Amit Nathwani, Dagmar Stoiber, Jan Spanholtz, Emilio Casanova, Erhard Hofer
We identified ZNF683/HOBIT as the most highly upregulated transcription factor gene during ex vivo differentiation of human CD34(+) cord blood progenitor cells to CD56(+) natural killer (NK) cells. ZNF683/HOBIT mRNA was preferentially expressed in NK cells compared to other human peripheral blood lymphocytes and monocytes. During ex vivo differentiation, ZNF683/HOBIT mRNA started to increase shortly after addition of IL-15 and further accumulated in parallel to the generation of CD56(+) NK cells. shRNA-mediated knockdown of ZNF683/HOBIT resulted in a substantial reduction of CD56(-)CD14(-) NK-cell progenitors and the following generation of CD56(+) NK cells was largely abrogated...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28533779/cytomegalovirus-driven-adaptive-like-natural-killer-cell-expansions-are-unaffected-by-concurrent-chronic-hepatitis-virus-infections
#14
David F G Malone, Sebastian Lunemann, Julia Hengst, Hans-Gustaf Ljunggren, Michael P Manns, Johan K Sandberg, Markus Cornberg, Heiner Wedemeyer, Niklas K Björkström
Adaptive-like expansions of natural killer (NK) cell subsets are known to occur in response to human cytomegalovirus (CMV) infection. These expansions are typically made up of NKG2C(+) NK cells with particular killer-cell immunoglobulin-like receptor (KIR) expression patterns. Such NK cell expansion patterns are also seen in patients with viral hepatitis infection. Yet, it is not known if the viral hepatitis infection promotes the appearance of such expansions or if effects are solely attributed to underlying CMV infection...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28505602/unusual-antigen-presentation-offers-new-insight-into-hiv-vaccine-design
#15
REVIEW
Andrew J McMichael, Louis J Picker
Recent findings with a rhesus monkey cytomegalovirus based simian immunodeficiency virus vaccine have identified strong CD8+ T cell responses that are restricted by MHC-E. Also mycobacteria specific CD8+ T cells, that are MHC-E restricted, have been identified. MHC-E therefore can present a wide range of epitope peptides to CD8+ T cells, alongside its well defined role in presenting a conserved MHC-class I signal peptide to the NKG2A/C-CD94 receptor on natural killer cells. Here we explore the antigen processing pathways involved in these atypical T cell responses...
June 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28481352/partial-break-in-tolerance-of-nkg2a-lir-1-single-kir-nk-cells-early-in-the-course-of-hla-matched-kir-mismatched-hematopoietic-cell-transplantation
#16
S Rathmann, C Keck, C Kreutz, N Weit, M Müller, J Timmer, S Glatzel, M Follo, M Malkovsky, M Werner, R Handgretinger, J Finke, P Fisch
Natural killer (NK) cell subpopulations from 8 HLA-matched but killer cell immunoglobulin-like receptor (KIR)/HLA-ligand-mismatched patient-donor pairs were analyzed in the course of allogeneic hematopoietic stem cell transplantation (HCT). The patients' post-transplantation NKG2A(-)/LIR-1(-) NK cells, which expressed only inhibitory KIRs for which the patient had no HLA class I ligands, showed higher cytotoxic capacity than the NKG2A(-)/LIR-1(-) NK cells lacking any inhibitory KIRs that remained tolerant throughout the course of HCT...
August 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28475642/mhc-ib-molecule-qa-1-presents-mycobacterium-tuberculosis-peptide-antigens-to-cd8-t-cells-and-contributes-to-protection-against-infection
#17
Yao Bian, Shaobin Shang, Sarah Siddiqui, Jie Zhao, Simone A Joosten, Tom H M Ottenhoff, Harvey Cantor, Chyung-Ru Wang
A number of nonclassical MHC Ib molecules recognizing distinct microbial antigens have been implicated in the immune response to Mycobacterium tuberculosis (Mtb). HLA-E has been identified to present numerous Mtb peptides to CD8+ T cells, with multiple HLA-E-restricted cytotoxic T lymphocyte (CTL) and regulatory T cell lines isolated from patients with active and latent tuberculosis (TB). In other disease models, HLA-E and its mouse homolog Qa-1 can act as antigen presenting molecules as well as regulators of the immune response...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28474506/expression-of-the-inhibitory-receptor-nkg2a-correlates-with-increased-liver-and-splenic-nk-cell-response-to-activating-receptor-engagement
#18
Claire E Meyer, Phillip N Key, Toby Zhu, Mark Shabsovich, Ann Ni, Sandeep K Tripathy
INTRODUCTION: Natural killer (NK) cells play a critical role in the innate immune response to viruses and tumors, and comprise a large proportion of the hepatic lymphocyte population. They must remain tolerant to non-pathogenic antigens while protecting the host from harmful agents. Herein, we investigate how the NK cell response to activation receptor engagement is altered in the liver. METHODS: In this study, we assess IFN-γ production and degranulation of splenic NK cells and selected subsets of liver NK cells...
June 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28450865/distinct-effects-of-dexamethasone-on-human-natural-killer-cell-responses-dependent-on-cytokines
#19
David J Morgan, Daniel M Davis
Glucocorticoids (GCs) have long been known to be immune suppressive and synthetic variants are widely used in the treatment of inflammatory disorders. Here, we report that, while suppressing the initial production of interferon-γ (IFN-γ), the synthetic GC dexamethasone (Dex) enhances the proliferation and survival of natural killer (NK) cells stimulated with interleukin-2 (IL-2) + interleukin-12 (IL-12). Inhibition of mTOR complex 1 by rapamycin revealed the immunosuppressive activity of Dex was independent from the effect of enhancing NK cell proliferation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28441851/-quantities-and-function-of-nk-cells-in-patients-with-immune-thrombocytopenia
#20
Y J Zhang, W Qu, H Liu, Y H Wang, C Y Liu, L J Li, H Q Wang, R Fu, L M Xing, Z H Shao
Objective: To investigate natural killer (NK) cell quantities and function in patients with immune thrombocytopenia (ITP) . Methods: A total of 66 ITP patients (34 newly diagnosed and 32 in complete remission) were collected from September 2015 to May 2016 in Tianjin Medical University General Hospital, and 30 healthy volunteers were recruited as controls. The percentages of NK cells and their subsets in peripheral blood, the expression of activating receptor (NKp44), inhibitory receptor (NKG2A) and CD16, perforin and granzyme β were detected by flow cytometry...
April 25, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
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