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https://www.readbyqxmd.com/read/28817402/the-importance-of-natural-killer-cell-killer-immunoglobulin-like-receptor-mismatch-in-transplant-outcomes
#1
Kate Stringaris, Austin J Barrett
PURPOSE OF REVIEW: In recent years, the rules of engagement between natural killer (NK) cells and their targets have become better defined with the identification of an array of NK surface molecules, notably the killer immunoglobulin-like (KIR) receptors and their ligands on target cells through which signals of activation or suppression of NK function are mediated. After allogeneic stem cell transplantation (SCT), the opportunity for NK cell activation can occur both in human leucocyte antigen (HLA) matched and HLA mismatched pairs...
August 16, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28815225/chronic-in-vivo-interaction-of-dendritic-cells-expressing-the-ligand-rae-1%C3%AE%C2%B5-with-nk-cells-impacts-nkg2d-expression-and-function
#2
Maelig G Morvan, Marine Champsaur, Boris Reizis, Lewis L Lanier
To investigate how dendritic cells (DCs) interact with NK cells in vivo, we developed a novel mouse model in which Rae-1ε, a ligand of the NKG2D receptor, is expressed in cells with high levels of CD11c. In these CD11c-Rae1 mice, expression of Rae-1 was confirmed on all subsets of DCs and a small subset of B and T cells, but not on NK cells. DC numbers and activation status were unchanged, and NK cells in these CD11c-Rae1 mice presented the same Ly49 repertoire and maturation levels as their littermate wildtype controls...
May 1, 2017: Immunohorizons
https://www.readbyqxmd.com/read/28815218/capturing-the-systemic-immune-signature-of-a-norovirus-infection-an-n-of-1-case-study-within-a-clinical-trial
#3
Antony J Cutler, Joao Oliveira, Ricardo C Ferreira, Ben Challis, Neil M Walker, Sarah Caddy, Jia Lu, Helen E Stevens, Deborah J Smyth, Marcin L Pekalski, Jane Kennet, Kara M D Hunter, Ian Goodfellow, Linda S Wicker, John A Todd, Frank Waldron-Lynch
BACKGROUND:  The infection of a participant with norovirus during the adaptive study of interleukin-2 dose on regulatory T cells in type 1 diabetes (DILT1D) allowed a detailed insight into the cellular and cytokine immune responses to this prevalent gastrointestinal pathogen. METHODS:  Serial blood, serum and peripheral blood mononuclear cell (PBMC) samples were collected pre-, and post-development of the infection. To differentiate between the immune response to norovirus and to control for the administration of a single dose of aldesleukin (recombinant interleukin-2, rIL-2) alone, samples from five non-infected participants administered similar doses were analysed in parallel...
2017: Wellcome Open Research
https://www.readbyqxmd.com/read/28814066/mice-expressing-human-erap1-variants-associated-with-ankylosing-spondylitis-have-altered-t-cell-repertoires-and-nk-cell-functions-as-well-as-increased-in-utero-and-perinatal-mortality
#4
David P W Rastall, Fadel S Alyaquob, Patrick O'Connell, Yuliya Pepelyayeva, Douglas Peters, Sarah Godbehere-Roosa, Cristiane Pereira-Hicks, Yasser A Aldhamen, Andrea Amalfitano
Specific variants of endoplasmic reticulum-associated aminopeptidase 1 (ERAP1) identified by genome-wide association study modify the risk for developing ankylosing spondylitis. We previously confirmed that disease-associated ERAP1 variants have altered enzymatic abilities that can impact upon the production of pro-inflammatory cytokines from cells expressing the same ERAP1 variants. To determine if these ERAP1 variants also impacted immune responses in vivo, we generated two strains of transgenic mice expressing human ERAP1 genes containing non-synonymous single-nucleotide polymorphisms associated with an increased (ERAP1-High) or decreased (ERAP1-Low) risk for developing autoimmune disease...
June 1, 2017: International Immunology
https://www.readbyqxmd.com/read/28812990/human-leukocyte-antigen-c-12-02-02-and-killer-immunoglobulin-like-receptor-2dl5-are-distinctly-associated-with-ankylosing-spondylitis-in-the-taiwanese
#5
Chin-Man Wang, Sheng-Hung Wang, Yeong-Jian Jan Wu, Jing-Chi Lin, Jianming Wu, Ji-Yih Chen
Human leukocyte antigen (HLA) class I ligands and Killer immunoglobulin-like receptors (KIRs) regulate the cytolytic activity of natural killer (NK) cells and certain T cells. We examined their genetic predisposition to disease susceptibility and clinical phenotypes in Taiwanese ankylosing spondylitis (AS) patients. KIR genotyping and Human Leucocyte Antigen C (HLA-C) sequencing were performed in 653 Taiwanese AS patients and 952 healthy controls. KIR genotype distributions and HLA-C allele frequencies were compared in patients and controls and among patients with and without HLA-B27 positivity, early age onset and spinal syndesmophytes...
August 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28812434/-pemetrexed-sildenafil-via-autophagy-dependent-hdac-down-regulation-enhances-the-immunotherapy-response-of-nsclc-cells
#6
Laurence Booth, Jane L Roberts, Andrew Poklepovic, Paul Dent
Pemetrexed is an approved therapeutic in NSCLC and ovarian cancer. Our studies focused on the ability of [pemetrexed + sildenafil] exposure to alter the immunogenicity of lung and ovarian cancer cells. Treatment of lung and ovarian cancer cells with [pemetrexed + sildenafil] in vitro rapidly reduced the expression of PD-L1, PD-L2 and ornithine decarboxylase (ODC), and increased the expression of Class I MHCA. In a cell-specific fashion, some cells also released the immunogenic nuclear protein HMGB1 into the extracellular environment...
August 16, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28811973/nk-cell-dysfunction-in-chronic-lymphocytic-leukemia-is-associated-with-loss-of-the-mature-cells-expressing-inhibitory-killer-cell-ig-like-receptors
#7
Alexander W MacFarlane, Mowafaq Jillab, Mitchell R Smith, R Katherine Alpaugh, Marion E Cole, Samuel Litwin, Michael M Millenson, Tahseen Al-Saleem, Adam D Cohen, Kerry S Campbell
A prospective analysis of natural killer (NK) cell phenotype and function was performed on fresh peripheral blood samples from untreated patients with B-cell chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Compared to healthy controls, CD56(dim) NK cells in CLL patients displayed reduced expression of the NKG2D activating receptor and increased CD27 expression, which indicates declines in mature cells. In addition, NK cells from CLL patients showed reduced degranulation responses toward transformed B cells alone or with rituximab and were more sensitive to activation-induced cell death...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811289/primary-tumors-limit-metastasis-formation-through-induction-of-il15-mediated-crosstalk-between-patrolling-monocytes-and-nk-cells
#8
Hiroshi Kubo, Sofia Mensurado, Natacha Goncalves-Sousa, Karine Serre, Bruno Silva-Santos
Metastases are responsible for the vast majority of cancer-related deaths. Although tumor cells can become invasive early during cancer progression, metastases formation typically occurs as a late event. How the immune response to primary tumors may dictate this outcome remains poorly understood, which hampers our capacity to manipulate it therapeutically. Here we used a two-step experimental model, based on the highly aggressive B16F10 melanoma, that temporally segregates the establishment of primary tumors (subcutaneously) and the formation of lung metastases (from intravenous injection)...
August 15, 2017: Cancer Immunology Research
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
#9
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/28810809/optimization-of-human-nk-cell-manufacturing-fully-automated-separation-improved-i-ex-vivo-i-expansion-using-il-21-with-autologous-feeder-cells-and-generation-of-anti-cd123-car-expressing-effector-cells
#10
Stephan Klöß, Olaf Oberschmidt, Michael Morgan, Julia Dahlke, Lubomir Arseniev, Volker Huppert, Markus Granzin, Tanja Gardlowski, Nadine Matthies, Stefanie Soltenborn, Axel Schambach, Ulrike Koehl
BACKGROUND AND AIMS: The administration of ex-vivo expanded Natural killer (NK) cells as potential antitumor effector cells appears to be suitable for effector cell-based immunotherapies in high-risk cancer patients. However, the GMP-conform manufacturing of clinical-grade NK cells at sufficiently high numbers represent a great challenge. Therefore, we improved and optimized previous expansion protocols for those effector cells through the use of newly developed culture medium, IL-21 and autologous feeder cells...
August 16, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28805342/deletion-of-the-activating-nk-cell-receptor-nkg2d-accelerates-rejection-of-cardiac-allografts
#11
Cornelia Fabritius, Paul Viktor Ritschl, Thomas Resch, Mario Roth, Susanne Ebner, Julia Günther, Vanessa Mellitzer, Anh-Vu Nguyen, Johann Pratschke, Martina Sauter, Karin Klingel, Katja Kotsch
It has already been shown that neutralization of the activating NK cell receptor NKG2D in combination with co-stimulation blockade prolongs graft survival of vascularized transplants. In order to clarify the underlying cellular mechanisms, we transplanted complete MHC-disparate BALB/c-derived cardiac grafts into C57BL/6 wildtypes or mice deficient for NKG2D (Klrk1(-/-) ). Although median survival was eight days for both recipient groups, we detected already at day 5 post-transplantation significantly greater intragraft frequencies of NKp46(+) NK cells in Klrk1(-/-) recipients than in wildtypes...
August 14, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28805308/lymphocyte-profile-and-cytokine-mrna-expression-in-peripheral-blood-mononuclear-cells-of-patients-with-recurrent-respiratory-papillomatosis-suggest-dysregulated-cytokine-mrna-response-and-impaired-cytotoxic-capacity
#12
Anna Holm, Olga Nagaeva, Ivan Nagaev, Christos Loizou, Göran Laurell, Lucia Mincheva-Nilsson, Karin Nylander, Katarina Olofsson
OBJECTIVES: Recurrent respiratory papillomatosis (RRP) is a relatively rare, chronic disease caused by Human Papilloma Virus (HPV) 6 and 11, and characterized by wart-like lesions in the airway affecting voice and respiratory function. The majority of HPV infections are asymptomatic and resolve spontaneously, however, some individuals are afflicted with persistent HPV infections. Failure to eliminate HPV 6 and 11 due to a defect immune responsiveness to these specific genotypes is proposed to play a major role in the development of RRP...
August 14, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28805233/analytic-and-dynamic-secretory-profile-of-patient-derived-cytokine-induced-killer-cells
#13
Giulia Mesiano, Roberta Zini, Giulia Montagner, Nicoletta Bianchi, Rossella Manfredini, Antonella Chillemi, Massimo Aglietta, Giovanni Grignani, Ilaria Lampronti, Erika Fiorino, Fabio Malavasi, Dario Sangiolo, Roberto Gambari, Davide Ferrari
Adoptive immunotherapy with Cytokine Induced Killer (CIK) cells has shown antitumor activity against several kinds of cancers in preclinical models and clinical trials. CIK cells are a subset of ex vivo expanded T lymphocytes with T-NK phenotype and MHC-unrestricted antitumor activity. Literature provides scanty information on cytokines, chemokines and growth factors secreted by CIK cells. Therefore, we investigated the secretory profile of CIK cells generated from tumor patients. The secretome analysis was performed at specific time points (day 1, day 14 and day 21) of CIK cells expansion...
August 9, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28804811/serum-diamine-oxidase-in-pseudoallergy-in-the-pediatric-population
#14
Joanna Kacik, Barbara Wróblewska, Sławomir Lewicki, Robert Zdanowski, Bolesław Kalicki
Histamine intolerance (pseudoallergy) is a poorly investigated type of food hypersensitivity. The main enzyme responsible for histamine degradation in the extracellular matrix is diamine oxidase (DAO). Disturbances in the concentration or activity of DAO may lead to the development of clinical signs of allergy. The aim of the present work was to assess the DAO concentration, peripheral blood morphology, lymphocytes phenotyping (CD3+, CD4+, CD8+, CD19+, NK cells, NKT cells, and activated T-cells), and natural regulatory Treg (nTregs) cell population (CD4+, CD25+, CD127low, and FoxP3) in 34 pediatric patients with histamine-dependent syndromes...
August 15, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28804584/the-expression-of-activating-receptor-gene-of-natural-killer-cells-klrc3-in-patients-with-%C3%A2-type-1-diabetes-mellitus-t1dm
#15
Dalia Shalaby, Marwa Saied, Doaa Khater, Abla Abou Zeid
OBJECTIVES: To identify the possible role of natural killer (NK) cells in the pathogenesis of type 1 diabetes mellitus (T1DM) through studying the expression of the KLRC3 gene, which encodes the NK cell activating receptor (NKG2E). METHODS: This study was conducted at Alexandria University Children's Hospital from April to October 2015. The study was conducted with 30 newly diagnosed T1DM patients (15 males and 15 females), aged 7-13 years (10.6±1.8 years) and 20 non-diabetic subjects served as age- and sex-matched controls...
July 2017: Oman Medical Journal
https://www.readbyqxmd.com/read/28803951/monocytes-inhibit-hepatitis-c-virus-induced-trail-expression-on-cd56-bright-nk-cells
#16
Dalila Mele, Stefania Mantovani, Barbara Oliviero, Giulia Grossi, Andrea Lombardi, Mario U Mondelli, Stefania Varchetta
BACKGROUND AND AIMS: Natural killer (NK) cells play an important role in the pathogenesis of HCV infection. We have previously shown that culture-derived HCV (HCVcc) enhance tumor necrosis-factor-related apoptosis-inducing ligand (TRAIL) expression on healthy but not on HCV-infected patient-derived NK cells, which was likely dependent on accessory cells. Here we sought mechanistic insights involved in altered TRAIL upregulation in this setting. METHODS: Peripheral blood mononuclear cells (PBMC) from controls and HCV-infected patients were exposed to HCVcc...
August 10, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28802832/retroviral-gene-transfer-into-primary-human-nk-cells-activated-by-il-2-and-k562-feeder-cells-expressing-membrane-bound-il-21
#17
Maria A Streltsova, Eugene Barsov, Sofia A Erokhina, Elena I Kovalenko
Natural killer (NK) cells are capable of rapidly recognizing and efficiently killing tumor cells. This makes them a potentially promising agent for cancer immunotherapy. Additional genetic modifications of NK cells may further improve their anti-tumor efficacy. Numerous technical challenges associated with gene delivery into NK cells have significantly tempered this approach. We achieved efficient retroviral vector transduction of primary human NK cells that were stimulated by a combination of IL-2 and engineered K562 cells expressing membrane-bound IL-21...
August 9, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28802736/synthesis-of-pegylated-polyglutamic-acid-peptide-dendrimer-and-its-application-in-dissolving-thrombus
#18
Shao-Fei Zhang, Chunmei Gao, Shaoyu Lü, Jiujun He, Mingzhu Liu, Can Wu, Yijing Liu, Xinyu Zhang, Zhen Liu
Nattokinase (NK) has been used as a new generation thrombolytic drug, due to its high safety, low cost and low side effects. However, it is sensitive to external environment and may lose the enzyme activity easily. Peptide dendrimer possesses functional groups on its surface, adjustable sizes, biodegradability, biocompatibility, and low toxicity, which could be used as ideal carrier for drug protection and delivery. Demonstrated for the first time in this paper, a PEGylated dendrimer (Gn-PEG-Gn) composed of polyglutamic acid is designed and synthesized as delivery platform of NK for thrombus treatment...
August 4, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28799796/immune-modulation-by-curcumin-the-role-of-interleukin-10
#19
Hamid Mollazadeh, Arrigo F G Cicero, Christopher N Blesso, Matteo Pirro, Muhammed Majeed, Amirhossein Sahebkar
Cytokines are small secreted proteins released by different types of cells with specific effects on cellular signaling and communication via binding to their receptors on the cell surface. IL-10 is known to be a pleiotropic and potent anti-inflammatory and immunosuppressive cytokine that is produced by both innate and adaptive immunity cells including dendritic cells, macrophages, mast cells, natural killer cells, eosinophils, neutrophils, B cells, CD8(+) T cells, and TH1, TH2, and TH17 and regulatory T cells...
August 11, 2017: Critical Reviews in Food Science and Nutrition
https://www.readbyqxmd.com/read/28795321/nkg2d-gene-polymorphisms-are-associated-with-disease-control-of-chronic-myeloid-leukemia-by-dasatinib
#20
Ryujiro Hara, Makoto Onizuka, Erika Matsusita, Eri Kikkawa, Yoshihiko Nakamura, Hiromichi Matsushita, Daisuke Ohgiya, Hiromichi Murayama, Shinichiro Machida, Ken Ohmachi, Yukari Shirasugi, Yoshiaki Ogawa, Hiroshi Kawada, Kiyoshi Ando
A recent study reported that treatment-free remission (TFR) of chronic myeloid leukemia (CML) after dasatinib (Das) treatment was significantly associated with natural killer (NK) cell proliferation in the peripheral blood. However, biomarkers to predict lymphocytosis or successful TFR are not well characterized. In order to clarify individual differences in NK cell responses among patients treated with Das, we retrospectively analyzed the association between polymorphisms in the natural killer group 2D receptor [NKG2D; also known as killer cell lectin like receptor K1 (KLRK1)] gene and clinical outcomes in 31 patients treated with Das as first-line treatment for CML...
August 9, 2017: International Journal of Hematology
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