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https://www.readbyqxmd.com/read/27903843/downregulation-of-l-arginine-metabolism-in-dendritic-cells-induces-tolerance-to-exogenous-antigen
#1
Patricia U Simioni, Luis Gr Fernandes, Wirla Msc Tamashiro
Dendritic cells (DC) are potential tools for therapeutic applications and several strategies to generate tolerogenic DCs are under investigation. When activated by cytokines and microbial products, DCs express mediators that modulate immune responses. In this regard, the metabolites generated by the activities of inducible nitric oxide synthase (iNOS) and arginase in DCs seem to play important roles. Here, we evaluated the effects of adoptive transfer of DCs generated in vitro from bone marrow precursors (BMDC) modulated with L-NAME (Nω-nitro-L-arginine methyl ester) and NOHA (NG-Hydroxy-L-arginine), inhibitors of iNOS and arginase, respectively, upon the immune response of the wild type (BALB/c) and OVA-TCR transgenic (DO11...
November 30, 2016: International Journal of Immunopathology and Pharmacology
https://www.readbyqxmd.com/read/27895174/human-lung-fibroblasts-present-bacterial-antigens-to-autologous-lung-th-cells
#2
Andrew J Hutton, Marta E Polak, C Mirella Spalluto, Joshua C Wallington, Chris Pickard, Karl J Staples, Jane A Warner, Tom M A Wilkinson
Lung fibroblasts are key structural cells that reside in the submucosa where they are in contact with large numbers of CD4(+) Th cells. During severe viral infection and chronic inflammation, the submucosa is susceptible to bacterial invasion by lung microbiota such as nontypeable Haemophilus influenzae (NTHi). Given their proximity in tissue, we hypothesized that human lung fibroblasts play an important role in modulating Th cell responses to NTHi. We demonstrate that fibroblasts express the critical CD4(+) T cell Ag-presentation molecule HLA-DR within the human lung, and that this expression can be recapitulated in vitro in response to IFN-γ...
November 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27895173/human-regulatory-t-cells-mediate-transcriptional-modulation-of-dendritic-cell-function
#3
Emily Mavin, Lindsay Nicholson, Syed Rafez Ahmed, Fei Gao, Anne Dickinson, Xiao-Nong Wang
Regulatory T cells (Treg) attenuate dendritic cell (DC) maturation and stimulatory function. Current knowledge on the functional impact of semimature DC is limited to CD4(+) T cell proliferation and cytokine production. Little is known about the molecular basis underpinning the functional effects of Treg-treated DC (Treg-DC). We present novel evidence that Treg-DC skewed CD4(+) naive T cell polarization toward a regulatory phenotype and impaired CD8(+) T cell allo-reactive responses, including their ability to induce target tissue damage in a unique in vitro human graft-versus-host disease skin explant model...
November 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27895172/pulmonary-dendritic-cell-subsets-shape-the-respiratory-syncytial-virus-specific-cd8-t-cell-immunodominance-hierarchy-in-neonates
#4
Allison M W Malloy, Tracy J Ruckwardt, Kaitlyn M Morabito, Annie W Lau-Kilby, Barney S Graham
Young infants are generally more susceptible to viral infections and experience more severe disease than do adults. CD8(+) T cells are important for viral clearance, and although often ineffective in neonates they can be protective when adequately stimulated. Using a murine CB6F1/J hybrid model of respiratory syncytial virus (RSV) infection, we previously demonstrated that the CD8(+) T cell immunodominance hierarchy to two RSV-derived epitopes, K(d)M282-90 and D(b)M187-195, was determined by the age at infection...
November 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27881707/a-cd80-biased-ctla4-ig-fusion-protein-with-superior-in-vivo-efficacy-by-simultaneous-engineering-of-affinity-selectivity-stability-and-fcrn-binding
#5
Julie Douthwaite, Jacques Moisan, Cyril Privezentzev, Blagoje Soskic, Shereen Sabbah, Suzanne Cohen, Andie Collinson, Elizabeth England, Catherine Huntington, Ben Kemp, Li Zhuang, Suzanne Hudak, D Gareth Rees, Debbie Goldberg, Chris Barton, Linda Chang, Inna Vainshtein, Meina Liang, Laurie Iciek, Philip Ambery, Mark Peakman, Tristan J Vaughan, Tim I M Tree, David M Sansom, Michael A Bowen, Ralph R Minter, Lutz Jermutus
Affinity- and stability-engineered variants of CTLA4-Ig fusion molecules with enhanced pharmacokinetic profiles could yield improved therapies with the potential of higher efficacy and greater convenience to patients. In this study, to our knowledge, we have, for the first time, used in vitro evolution to simultaneously optimize CTLA4 affinity and stability. We selected for improved binding to both ligands, CD80 and CD86, and screened as dimeric Fc fusions directly in functional assays to identify variants with stronger suppression of in vitro T cell activation...
November 23, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27867516/autoantibodies-against-cd80-in-patients-with-copd
#6
Xu Min Luo, Xin Yan Liu, Ji Hong Tang, Wei Yang, Zhen Hua Ni, Qing Ge Chen, Xiongbiao Wang
Chronic obstructive pulmonary disease (COPD) is an inflammation disorder and possibly an autoimmune disease. The components of the autoimmune response in the circulatory system are of considerable interest to clinicians. Because aberrations of costimulation status have been noted in COPD, the presence of autoantibodies to B7 costimulatory factor CD80 were investigated in a cohort of patients. Recombinant rs1CD80 (lacking the transmembrane domain of CD80) was used for Western blot analysis and ELISA to investigate the presence of autoantibodies in sera of patients with stable COPD and in controls without COPD...
October 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/27865860/human-regulatory-b-cells-control-tfh-response
#7
Achouak Achour, Quentin Simon, Audrey Mohr, Jean-François Séité, Pierre Youinou, Boutahar Bendaoud, Ibtissem Ghedira, Jacques-Olivier Pers, Christophe Jamin
BACKGROUND: Follicular helper T (Tfh) cells support the terminal B-cell differentiation. Human regulatory B (Breg) cells modulate cellular responses but their control of Tfh-dependent humoral immune responses is unknown. OBJECTIVE: To assess the role of Breg cells on Tfh development and function. METHODS: Human T cells were polyclonally stimulated in the presence of IL-12 and IL-21 to generate Tfh cells. They were co-cultured with B cells to induce their terminal differentiation...
November 16, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27863548/impact-of-in-vitro-treatments-of-physiological-levels-of-estradiol-and-progesterone-observed-in-pregnancy-on-bovine-monocyte-derived-dendritic-cell-differentiation-and-maturation
#8
Brianna Pomeroy, Suzanne Klaessig, Ynte Schukken
The specific factors which regulate differentiation and maturation of dendritic cells in bovine pregnancy remain unclear. We evaluated the influence of physiologically relevant in vitro treatments of progesterone (PG) and estradiol (E2) observed in late pregnancy on the differentiation and maturation of CD14+ monocyte-derived dendritic cell (moDC) from non-pregnant, lactating dairy cows (n=7). We found that moDC differentiated in the presence of both E2 and PG had impaired E. coli-induced phenotypic maturation, specifically a significant reduction in CD80 and MHC II expression...
December 2016: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/27862204/a-comparison-of-the-immunological-potency-of-burkholderia-lipopolysaccharides-in-endotoxemic-balb-c-mice
#9
Pei-Tan Hsueh, Chiu-Lin Liu, Hsuan-Han Wang, Wei-Fan Ni, Ya-Lei Chen, Jong-Kang Liu
Lipopolysaccharide (LPS) is one of virulence factors of the soil-borne pathogens Burkholderia pseudomallei (Bp), B. thailandensis (Bt), B. cenocepacia (Bc) and B. multivorans (Bm) that cause septic melioidosis (often in Bp infections but rarely in Bt infections) or cepacia syndromes (commonly in Bc infections but rarely in Bm infections). The inflammatory responses in Burkholderia LPS-induced endotoxemia were evaluated in this study. Prior to an induction, the conserved structures and functions of each purified LPS were confirmed using electrophoretic phenotypes, the ratios of 3-hydroxytetradecanoic to 3-hydroxyhexadecanoic acid and the endotoxin units...
November 8, 2016: Microbiology and Immunology
https://www.readbyqxmd.com/read/27862100/role-of-epigenetic-modification-and-immunomodulation-in-a-murine-prostate-cancer-model
#10
Jay E Sulek, Samuel P Robinson, Albert A Petrossian, Shaoqing Zhou, Ekaterine Goliadze, Masoud H Manjili, Amir Toor, Georgi Guruli
INTRODUCTION: Decreased expression of highly immunogenic cancer-testis antigens (CTA) might help tumor to achieve low immunogenicity, escape immune surveillance and grow unimpeded. Our aim was to evaluate CTA expression in tumor and normal tissues and to investigate possible means of improving the immune response in a murine prostate cancer (CaP) model by using the combination of epigenetic modifier 5-azacitidine (5-AzaC) and immunomodulator lenalidomide. No study to date has examined the effect of this combination on the prostate cancer or its impact on antigen-presenting cells (APC)...
November 8, 2016: Prostate
https://www.readbyqxmd.com/read/27861289/the-effect-of-asp2409-a-novel-cd86-selective-variant-of-ctla4-ig-on-renal-allograft-rejection-in-nonhuman-primates
#11
Shinsuke Oshima, Erik E Karrer, Yuka Kawato, Masashi Maeda, Hidehiko Fukahori, Susumu Tsujimoto, Jun Hirose, Koji Nakamura, Takanori Marui, Fujiko Takamura, Takahisa Noto, Steven J Chapin, Yasutomo Fujii, Margaret Neighbors, Sridhar Viswanathan, Bruce H Devens, Yasuyuki Higashi
BACKGROUND: Blockade of CD28-mediated T cell costimulation by a modified cytotoxic T lymphocyte-associated antigen 4 (CTLA4-Ig), belatacept, is a clinically effective immunosuppressive therapy for the prevention of renal allograft rejection. Use of belatacept-based calcineurin inhibitor-free immunosuppression, however, has demonstrated an increased frequency of cellular rejection episodes and immunosuppression-related safety issues relative to conventional regimens. Furthermore, belatacept typically requires infusion for its administration chronically, which may present an inconvenience to patients...
December 2016: Transplantation
https://www.readbyqxmd.com/read/27857057/in-vitro-exploration-of-a-myeloid-derived-suppressor-cell-line-as-vehicle-for-cancer-gene-therapy
#12
S Denies, F Combes, C Ghekiere, S Mc Cafferty, L Cicchelero, N N Sanders
Recent research indicates that cell-mediated gene therapy can be an interesting method to obtain intratumoral expression of therapeutic proteins. This paper explores the possibility of using transfected myeloid-derived suppressor cells (MDSCs), derived from a murine cell line, as cellular vehicles for transporting plasmid DNA (pDNA) encoding interleukin-12 (IL-12) to tumors. Transfecting these cells via electroporation caused massive cell death. This was not due to electroporation-induced cell damage, but was mainly the result of the intracellular presence of plasmids...
November 18, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27849166/first-in-human-study-in-healthy-subjects-with-fr104-a-pegylated-monoclonal-antibody-fragment-antagonist-of-cd28
#13
Nicolas Poirier, Gilles Blancho, Maryvonne Hiance, Caroline Mary, Tim Van Assche, Jos Lempoels, Steven Ramael, Weirong Wang, Virginie Thepenier, Cecile Braudeau, Nina Salabert, Regis Josien, Ian Anderson, Ian Gourley, Jean-Paul Soulillou, Didier Coquoz, Bernard Vanhove
FR104 is a monovalent pegylated Fab' Ab, antagonist of CD28, under development for treatment of transplant rejection and autoimmune diseases. In contrast to CD80/86 antagonists (CTLA4-Ig), FR104 selectively blunts CD28 costimulation while sparing CTLA-4 and PD-L1 coinhibitory signals. In the present work, FR104 has been evaluated in a first-in-human study to evaluate the safety, pharmacokinetics, pharmacodynamics, and potency of i.v. administrations in healthy subjects. Sixty-four subjects were randomly assigned to four single ascending dose groups, two double dose groups and four single ascending dose groups challenged with keyhole limpet hemocyanin...
November 14, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27843708/prospective-preliminary-in-vitro-investigation-of-a-magnetic-iron-oxide-nanoparticle-conjugated-with-ligand-cd80-and-vegf-antibody-as-a-targeted-drug-delivery-system-for-the-induction-of-cell-death-in-rodent-osteosarcoma-cells
#14
AnneMarie Kay Kovach, Jen M Gambino, Vina Nguyen, Zach Nelson, Taylor Szasz, Jun Liao, Lakiesha Williams, Sandra Bulla, Raj Prabhu
Target drug deliveries using nanotechnology are a novel consideration in the treatment of cancer. We present herein an in vitro mouse model for the preliminary investigation of the efficacy of an iron oxide nanoparticle complex conjugated to vascular endothelial growth factor (VEGF) antibody and ligand cluster of differentiation 80 (CD80) for the purpose of eventual translational applications in the treatment of human osteosarcoma (OSA). The 35 nm diameter iron oxide magnetic nanoparticles are functionalized with an n-hydroxysuccinimide biocompatible coating and are conjugated on the surface to proteins VEGF antibody and ligand CD80...
2016: BioResearch Open Access
https://www.readbyqxmd.com/read/27835062/class-i-restricted-t-cell-associated-molecule-is-a-marker-for-ifn-%C3%AE-producing-inkt-cells-in-healthy-subjects-and-patients-with-type-1-diabetes
#15
Nonantzin Beristain-Covarrubias, Elsy B Canche-Pool, Carlos Ramirez-Velazquez, Juan Carlos Barragan-Galvez, Rita A Gomez-Diaz, Vianney Ortiz-Navarrete
Class I-restricted T cell-associated molecule (CRTAM) is an activation marker expressed on the cell surface of activated invariant natural killer T (iNKT) cells, CD8(+) T cells, and a small subset of CD4(+) T cells. CRTAM has also been associated with a proinflammatory profile in murine CD4(+) T cells. However, CRTAM has not been thoroughly explored in human cells. This work focused on evaluating CRTAM expression in human iNKT lymphocytes after activation with α-galactosylceramide, its widely used specific glycolipid antigen...
November 11, 2016: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/27833846/mesenchymal-stromal-cells-derived-from-whole-human-umbilical-cord-exhibit-similar-properties-to-those-derived-from-wharton-s-jelly-and-bone-marrow
#16
Claire Mennan, Sharon Brown, Helen McCarthy, Eleni Mavrogonatou, Dimitris Kletsas, John Garcia, Birender Balain, James Richardson, Sally Roberts
Mesenchymal stromal cells (MSC) can be isolated from several regions of human umbilical cords, including Wharton's jelly (WJ), artery, vein or cord lining. These MSC appear to be immune privileged and are promising candidates for cell therapy. However, isolating MSC from WJ, artery, vein or cord lining requires time-consuming tissue dissection. MSC can be obtained easily via briefly digesting complete segments of the umbilical cord, likely containing heterogenous or mixed populations of MSC (MC-MSC). MC-MSC are generally less well characterized than WJ-MSC, but nevertheless represent a potentially valuable population of MSC...
November 2016: FEBS Open Bio
https://www.readbyqxmd.com/read/27832318/immunological-effects-of-a-novel-rna-based-adjuvant-in-liver-cancer-patients
#17
Luisa Circelli, Annacarmen Petrizzo, Maria Tagliamonte, Regina Heidenreich, Maria Lina Tornesello, Franco M Buonaguro, Luigi Buonaguro
Evaluation of biological effects of adjuvants on immune cells has been assessed in a limited number of studies. Moreover, no data are available on samples derived from cancer patients who may have a severe immune impairment. The effects of a novel RNA-based adjuvant (RNAdjuvant(®) developed by CureVac) were assessed in an ex vivo setting on PBMCs obtained from 8 healthy volunteers and 17 HCC patients, using a multiparametric approach to analyze network dynamics of early immune responses. Evaluation of CD80, CD86 and HLA-DR expression, cytokine production as well as gene expression was performed...
November 10, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27827885/is-there-still-room-for-cancer-vaccines-at-the-era-of-checkpoint-inhibitors
#18
REVIEW
Soumaya Karaki, Marie Anson, Thi Tran, Delphine Giusti, Charlotte Blanc, Stephane Oudard, Eric Tartour
Checkpoint inhibitor (CPI) blockade is considered to be a revolution in cancer therapy, although most patients (70%-80%) remain resistant to this therapy. It has been hypothesized that only tumors with high mutation rates generate a natural antitumor T cell response, which could be revigorated by this therapy. In patients with no pre-existing antitumor T cells, a vaccine-induced T cell response is a rational option to counteract clinical resistance. This hypothesis has been validated in preclinical models using various cancer vaccines combined with inhibitory pathway blockade (PD-1-PDL1-2, CTLA-4-CD80-CD86)...
November 3, 2016: Vaccines
https://www.readbyqxmd.com/read/27822406/pd-1-inhibition-and-treatment-of-advanced-melanoma-role-of-pembrolizumab
#19
REVIEW
Ali R Jazirehi, Alexandra Lim, Tam Dinh
Remarkable clinical responses have been seen in patients with metastatic melanoma with targeted therapy (BRAFi vemurafenib, MEKi) and with modern immune cell-based approaches such as TCR engineered adoptive cell transfer (ACT) and earlier experiences with high-dose IL-2. The proximal mediators of these immune therapies are tumor-reactive CTL. Various mechanisms of resistance to immune-mediated apoptotic signals have been described, including phenotypic changes, effector cell exhaustion, functional tolerance, deficiencies in Ag processing and presentation, and mutation or down-regulation of antigenic epitopes...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27815447/efficient-culture-of-human-naive-and-memory-b-cells-for-use-as-apcs
#20
Kuei-Ying Su, Akiko Watanabe, Chen-Hao Yeh, Garnett Kelsoe, Masayuki Kuraoka
The ability to culture and expand B cells in vitro has become a useful tool for studying human immunity. A limitation of current methods for human B cell culture is the capacity to support mature B cell proliferation. We developed a culture method to support the efficient activation and proliferation of naive and memory human B cells. This culture supports extensive B cell proliferation, with ∼10(3)-fold increases following 8 d in culture and 10(6)-fold increases when cultures are split and cultured for 8 more days...
November 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
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