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https://www.readbyqxmd.com/read/29459477/intrinsic-functional-potential-of-nk-cell-subsets-constrains-retargeting-driven-by-chimeric-antigen-receptors
#1
Vincent Yi Sheng Oei, Marta Siernicka, Agnieszka Graczyk-Jarzynka, Hanna Julie Hoel, Weiwen Yang, Daniel Palacios, Hilde Almasbak, Malgorzata Bajor, Dennis Clement, Ludwig Brandt, Bjorn Onfelt, 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 2nd- and 3rd-generation anti-CD19 CAR constructs with different signaling domains and spacer regions, a 3rd-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
#2
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
#3
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
#4
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, -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
#5
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
#6
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-nk-and-t-cells-differential-surface-expression-of-kir-receptors
#7
Ariel Podhorzer, Andrés Machicote, Santiago Belen, 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 NK, 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 activatory 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-cd56dim-natural-killer-cells
#8
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 (CD56brightCD16-/dim) and produces IFN-γ in response to cytokine stimulation, whereas the mature CD56dimCD16+ 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
#9
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
#10
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
https://www.readbyqxmd.com/read/29042861/corrigendum-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
#11
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, Maite Teresa 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, Nima Parvaneh, Alessandro Plebani, Susan Prockop, Ismail Reisli, Jian Yi Soh, Raz Somech, Troy R Torgerson, Yae-Jean Kim, Jolan E Walter, Andrew R Gennery, Sevgi Keles, John P Manis, Emanuela Marcenaro, Alessandro Moretta, Silvia Parolini, Luigi D Notarangelo
[This corrects the article on p. 798 in vol. 8, PMID: 28769923.].
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29023581/activating-and-inhibitory-receptors-on-natural-killer-cells-in-patients-with-systemic-lupus-erythematosis-regulation-with-interleukin-15
#12
Syh-Jae Lin, Ming-Ling Kuo, Hsiu-Shan Hsiao, Pei-Tzu Lee, Ji-Yih Chen, Jing-Long Huang
Natural killer (NK) cells may play an important role in the pathogenesis of SLE. Interleukin(IL)-15, an NK-enhancing cytokine, is over-expressed in SLE patients. In the present study, we examined the effect of IL-15 on NK cytotoxicity of SLE patients, and the expression of various activating and inhibitory NK receptors on NK cells from SLE patients in relation to disease activity. We also sought to determine how IL-15 would affect the NK receptor expression on NK cells from SLE patients. PBMCs were collected from 88 SLE patients with inactive disease activity (SLEDAI score<6) and active disease activity (SLEDAI score≥6), 26 age-matched healthy adults were used as controls...
2017: PloS One
https://www.readbyqxmd.com/read/28987965/emerging-targets-in-cancer-immunotherapy
#13
REVIEW
Samantha Burugu, Amanda R Dancsok, Torsten O Nielsen
The first generation of immune checkpoint inhibitors (anti-CTLA-4 and anti-PD-1/PD-L1) targeted natural immune homeostasis pathways, co-opted by cancers, to drive anti-tumor immune responses. These agents led to unprecedented results in patients with previously incurable metastatic disease and may become first-line therapies for some advanced cancers. However, these agents are efficacious in only a minority of patients. Newer strategies are becoming available that target additional immunomodulatory mechanisms to activate patients' own anti-tumor immune responses...
October 5, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28986344/nk-cell-recovery-after-haploidentical-hsct-with-post-transplant-cyclophosphamide-dynamics-and-clinical-implications
#14
Antonio Russo, Giacomo Oliveira, Sofia Berglund, Raffaella Greco, Valentina Gambacorta, Nicoletta Cieri, Cristina Toffalori, Laura Zito, Francesca Lorentino, Simona Piemontese, Mara Morelli, Fabio Giglio, Andrea Assanelli, Maria Teresa Lupo Stanghellini, Chiara Bonini, Jacopo Peccatori, Fabio Ciceri, Leo Luznik, Luca Vago
The use of post-transplant cyclophosphamide (PT-Cy) as GvHD prophylaxis has revolutionized haploidentical HSCT, allowing safe infusion of unmanipulated T cell-replete grafts. PT-Cy selectively eliminates proliferating alloreactive T cells, but whether and how it affects NK cells and their alloreactivity is largely unknown. Here we characterized NK cell dynamics in 17 patients who received unmanipulated haploidentical grafts, containing high numbers of mature NK cells, according to PT-Cy-based protocols in two independent centers...
October 6, 2017: Blood
https://www.readbyqxmd.com/read/28979268/nkg2c-nkg2a-natural-killer-cells-are-associated-with-a-lower-viral-set-point-and-may-predict-disease-progression-in-individuals-with-primary-hiv-infection
#15
Meichen Ma, Zhuo Wang, Xi Chen, Anfu Tao, Lei He, Shuai Fu, Zining Zhang, Yajing Fu, Chenxi Guo, Jing Liu, Xiaoxu Han, Junjie Xu, Zhenxing Chu, Haibo Ding, Hong Shang, Yongjun Jiang
Natural killer (NK) cells are the first line of defense against pathogens of the immune system and also play an important role in resistance against HIV. The activating receptor NKG2C and the inhibitory receptor NKG2A co-modulate the function of NK cells by recognizing the same ligand, HLA-E. However, the role of NKG2A and NKG2C on viral set point and the prediction of HIV disease progression have been rarely reported. In this study, we determined the expression of NKG2C or NKG2A on the surface of NK cells from 22 individuals with primary HIV infection (PHI) stage and 23 HIV-negative normal control (NC) subjects...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28870891/lidocaine-stimulates-the-function-of-natural-killer-cells-in-different-experimental-settings
#16
REVIEW
Juan P Cata, Maria F Ramirez, Jose F Velasquez, A I Di, Keyuri U Popat, Vijaya Gottumukkala, Dahlia M Black, Valerae O Lewis, Jean N Vauthey
BACKGROUND: One of the functions of natural killer (NK) cells is to eliminate cancer cells. The cytolytic activity of NK cells is tightly regulated by inhibitory and activation receptors located in the surface membrane. Lidocaine stimulates the function of NK cells at clinically relevant concentrations. It remains unknown whether this effect of lidocaine has an impact on the expression of surface receptors of NK cells, can uniformly stimulate across different cancer cell lines, and enhances the function of cells obtained during oncological surgery...
September 2017: Anticancer Research
https://www.readbyqxmd.com/read/28835490/asymptomatic-primary-infection-with-epstein-barr-virus-observations-on-young-adult-cases
#17
Rachel J Abbott, Annette Pachnio, Isabela Pedroza-Pacheco, Alison M Leese, Jusnara Begum, Heather M Long, Debbie Croom-Carter, Andrea Stacey, Paul A H Moss, Andrew D Hislop, Persephone Borrow, Alan B Rickinson, Andrew I Bell
Epstein-Barr virus (EBV) is typically acquired asymptomatically in childhood. In contrast, infection later in life often leads to infectious mononucleosis (IM), a febrile illness characterized by anti-EBV IgM antibody positivity, high loads of circulating latently infected B cells, and a marked lymphocytosis caused by hyperexpansion of EBV-specific CD8(+) T cells plus a milder expansion of CD56(dim) NKG2A(+) KIR(-) natural killer (NK) cells. How the two situations compare is unclear due to the paucity of studies on clinically silent infection...
November 1, 2017: Journal of Virology
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
#18
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
#19
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
#20
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
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