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https://www.readbyqxmd.com/read/28446441/long-term-persistence-of-cell-mediated-and-humoral-responses-to-a-h1n1-pdm09-influenza-virus-vaccines-and-the-role-of-the-as03-adjuvant-system-in-adults-during-two-randomized-controlled-trials
#1
Robbert G van der Most, Frédéric Clément, Julie Willekens, Walthère Dewé, Karl Walravens, David W Vaughn, Geert Leroux-Roels
We investigated the role of AS03, an α-tocopherol oil-in-water-emulsion-based Adjuvant System, on the long-term persistence of humoral and cell-mediated immune responses to A(H1N1)pdm09 influenza vaccines. In two studies (NCT00968539/NCT00989287), a total of 261 healthy adults (age ≤60 years) were randomized to receive two doses of AS03-adjuvanted vaccine containing 3.75 μg hemagglutinin, or non-adjuvanted vaccine containing 15 μg hemagglutinin (in Study A) or 3.75 μg hemagglutinin (in Study B), 21 days apart...
April 26, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28446245/mining-a-differential-sialotranscriptome-of-rhipicephalus-microplus-guides-antigen-discovery-to-formulate-a-vaccine-that-reduces-tick-infestations
#2
Sandra R Maruyama, Gustavo R Garcia, Felipe R Teixeira, Lucinda G Brandão, Jennifer M Anderson, José M C Ribeiro, Jesus G Valenzuela, Jana Horackova, Cecília J Veríssimo, Luciana M Katiki, Tamy M Banin, Amanda F Zangirolamo, Luiz G Gardinassi, Beatriz R Ferreira, Isabel K F de Miranda-Santos
BACKGROUND: Ticks cause massive damage to livestock and vaccines are one sustainable substitute for the acaricides currently heavily used to control infestations. To guide antigen discovery for a vaccine that targets the gamut of parasitic strategies mediated by tick saliva and enables immunological memory, we exploited a transcriptome constructed from salivary glands from all stages of Rhipicephalus microplus ticks feeding on genetically tick-resistant and susceptible bovines. RESULTS: Different levels of host anti-tick immunity affected gene expression in tick salivary glands; we thus selected four proteins encoded by genes weakly expressed in ticks attempting to feed on resistant hosts or otherwise abundantly expressed in ticks fed on susceptible hosts; these sialoproteins mediate four functions of parasitism deployed by male ticks and that do not induce antibodies in naturally infected, susceptible bovines...
April 26, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28446142/differences-in-peripheral-myelin-antigen-specific-t-cell-responses-and-t-memory-subsets-in-atypical-versus-typical-cidp
#3
M Staudt, J M Diederich, C Meisel, A Meisel, J Klehmet
BACKGROUND: Chronic inflammatory demyelinating polyneuropathy (CIDP) is presented by a large heterogeneity of clinical phenotypes. Around 50% of patients suffer from typical CIDP and show better therapy response than atypical variants. The goal of our study was to search for cellular immunological differences in typical versus atypical CIDP in comparison to controls. METHODS: We evaluated 26 (9 typical, 17 atypical) patients with mainly active-unstable CIDP using clinical and immunological examinations (enzyme-linked immunospot assay ELISPOT, fluorescence-activated cell sorting FACS) in comparison to 28 healthy, age-matched controls (HC)...
April 26, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28445512/proportions-of-circulating-follicular-helper-t-cells-are-reduced-and-correlate-with-memory-b-cells-in-hiv-infected-children
#4
Daniel M Muema, Gladys N Macharia, Babatunde A Olusola, Amin S Hassan, Greg W Fegan, James A Berkley, Britta C Urban, Eunice W Nduati
INTRODUCTION: HIV causes defects in memory B cells in children, but the mechanisms of those defects have not been fully elucidated. One possible mechanism is the lack of T-cell help to B cells during immune reactions. However, few studies have assessed the effect of HIV on follicular helper T cells (TFH cells) in children. METHODS: In this study, follicular-homing CD4 T cells and memory B cells were assessed in HIV-infected children and compared with children from the community...
2017: PloS One
https://www.readbyqxmd.com/read/28443098/the-lysine-methyltransferase-g9a-in-immune-cell-differentiation-and-function
#5
REVIEW
Sebastian Scheer, Colby Zaph
G9a (KMT1C, EHMT2) is a lysine methyltransferase (KMT) whose primary function is to di-methylate lysine 9 of histone H3 (H3K9me2). G9a-dependent H3K9me2 is associated with gene silencing and acts primarily through the recruitment of H3K9me2-binding proteins that prevent transcriptional activation. Gene repression via G9a-dependent H3K9me2 is critically required in embryonic stem (ES) cells for the development of cellular lineages by repressing expression of pluripotency factors. In the immune system, lymphoid cells such as T cells and innate lymphoid cells (ILCs) can differentiate from a naïve state into one of several effector lineages that require both activating and repressive mechanisms to maintain the correct gene expression program...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28443090/immunometabolic-regulations-mediated-by-coinhibitory-receptors-and-their-impact-on-t-cell-immune-responses
#6
REVIEW
Nikolaos Patsoukis, Jessica D Weaver, Laura Strauss, Christoph Herbel, Pankaj Seth, Vassiliki A Boussiotis
Host immunity provides wide spectrum protection that serves to eradicate pathogens and cancer cells, while maintaining self-tolerance and immunological homeostasis. Ligation of the T cell receptor (TCR) by antigen activates signaling pathways that coordinately induce aerobic glycolysis, mitochondrial activity, anabolic metabolism, and T effector cell differentiation. Activation of PI3K, Akt, and mTOR triggers the switch to anabolic metabolism by inducing transcription factors such as Myc and HIF1, and the glucose transporter Glut1, which is pivotal for the increase of glucose uptake after T cell activation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28441965/evaluation-of-a-dna-a%C3%AE-42-vaccine-in-adult-rhesus-monkeys-macaca-mulatta-antibody-kinetics-and-immune-profile-after-intradermal-immunization-with-full-length-dna-a%C3%AE-42-trimer
#7
Doris Lambracht-Washington, Min Fu, Pat Frost, Roger N Rosenberg
BACKGROUND: Aggregated amyloid-β peptide 1-42 (Aβ42), derived from the cellular amyloid precursor protein, is one of the pathological hallmarks of Alzheimer's disease (AD). Although active immunization against Aβ42 peptide was successful in AD mouse models and led to removal of plaques and improved memory, a similar clinical trial in humans (Aβ42 peptide immunization with QS-21 adjuvant) was stopped in phase II, when 6% of the treated patients developed encephalitis. Currently ongoing passive immunizations with the injection of preformed monoclonal antibodies against different epitopes within the Aβ1-42 peptide, which do not lead to activation of the immune system, have shown some effects in slowing AD pathology...
April 26, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28439570/epigenomics-of-human-cd8-t-cell-differentiation-and-aging
#8
David M Moskowitz, David W Zhang, Bin Hu, Sabine Le Saux, Rolando E Yanes, Zhongde Ye, Jason D Buenrostro, Cornelia M Weyand, William J Greenleaf, Jörg J Goronzy
The efficacy of the adaptive immune response declines dramatically with age, but the cell-intrinsic mechanisms driving immune aging in humans remain poorly understood. Immune aging is characterized by a loss of self-renewing naïve cells and the accumulation of differentiated but dysfunctional cells within the CD8 T cell compartment. Using ATAC-seq, we inferred the transcription factor binding activities correlated with naive and central and effector memory CD8 T cell states in young adults. Integrating our results with RNA-seq, we identified transcription networks associated with CD8 T cell differentiation, with prominent roles implicated for BATF, ETS1, Eomes, and Sp1...
February 2017: Science Immunology
https://www.readbyqxmd.com/read/28438506/diacylglycerol-kinase-%C3%AE-limits-cytokine-dependent-expansion-of-cd8-t-cells-with-broad-antitumor-capacity
#9
Elena Andrada, Rosa Liébana, Isabel Merida
Interleukin-2 and -15 drive expansion/differentiation of cytotoxic CD8(+) T cells that eliminate targets via antigen-independent killing. This property is clinically relevant for the improvement of T cell-based antitumor therapies. Diacylglycerol kinase α and ζ (DGKα/ζ) metabolize the diacylglycerol generated following antigen recognition by T lymphocytes. Enhanced expression of these two lipid kinases in tumor-infiltrating CD8(+) T cells promotes a hyporesponsive state that contributes to tumor immune escape...
April 14, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28436963/a-sting-activating-nanovaccine-for-cancer-immunotherapy
#10
Min Luo, Hua Wang, Zhaohui Wang, Haocheng Cai, Zhigang Lu, Yang Li, Mingjian Du, Gang Huang, Chensu Wang, Xiang Chen, Matthew R Porembka, Jayanthi Lea, Arthur E Frankel, Yang-Xin Fu, Zhijian J Chen, Jinming Gao
The generation of tumour-specific T cells is critically important for cancer immunotherapy. A major challenge in achieving a robust T-cell response is the spatiotemporal orchestration of antigen cross-presentation in antigen-presenting cells with innate stimulation. Here, we report a minimalist nanovaccine, comprising a simple physical mixture of an antigen and a synthetic polymeric nanoparticle, PC7A NP, which generates a strong cytotoxic T-cell response with low systemic cytokine expression. Mechanistically, the PC7A NP achieves efficient cytosolic delivery of tumour antigens to antigen-presenting cells in draining lymph nodes, leading to increased surface presentation while simultaneously activating type I interferon-stimulated genes...
April 24, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/28435676/understanding-cd8-t-cell-responses-toward-the-native-and-alternate-hla-a-02-01-restricted-wt1-epitope
#11
Thi Ho Nguyen, Amabel Cl Tan, Sue D Xiang, Anne Goubier, Kim L Harland, E Bridie Clemens, Magdalena Plebanski, Katherine Kedzierska
The Wilms' tumor 1 (WT1) antigen is expressed in solid and hematological malignancies, but not healthy tissues, making it a promising target for cancer immunotherapies. Immunodominant WT1 epitopes, the native HLA-A2/WT1126-134 (RMFPNAPYL) (HLA-A2/RMFPNAPYL epitope (WT1A)) and its modified variant YMFPNAPYL (HLA-A2/YMFPNAPYL epitope (WT1B)), can induce WT1-specific CD8(+) T cells, although WT1B is more stably bound to HLA-A*02:01. Here, to further determine the benefits of those two targets, we assessed the naive precursor frequencies; immunogenicity and cross-reactivity of CD8(+) T cells directed toward these two WT1 epitopes...
March 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28435674/the-three-rs-recruitment-retention-and-residence-of-leukocytes-in-the-liver
#12
REVIEW
Hayley A McNamara, Ian A Cockburn
The composition of leukocytes in the liver is highly distinct from that of the blood and lymphoid organs. In particular, the liver is highly enriched in non-conventional T cells such as natural killer T (NKT) cells, γδ T cells and mucosal-associated invariant T cells. In addition, there are significant populations of tissue-resident NK cells (or innate lymphoid cells (ILC1)) and memory CD8(+) T cells. These cells are joined in conditions of inflammation by neutrophils, monocytes and macrophages. In recent years a multitude of studies have generated insights into how these cells arrest, move and remain resident in the liver...
December 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28435008/cortical-and-amygdalar-neuronal-ensembles-in-alcohol-seeking-drinking-and-withdrawal
#13
REVIEW
Olivier George, Bruce T Hope
Alcohol induces many alterations in the brain that are thought to contribute to alcohol addiction. Most of the known alterations are induced in all neurons of a brain area or all neurons of a given cell type, regardless of whether they were activated during behavior. While these alterations can have important modulatory effects on behavior, they cannot explain why animals respond specifically to alcohol-paired cues as opposed to all other non-paired cues, and evoke highly specific goal-directed learned responses in models of drug craving...
April 20, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28434800/medial-entorhinal-cortex-selectively-supports-temporal-coding-by-hippocampal-neurons
#14
Nick T M Robinson, James B Priestley, Jon W Rueckemann, Aaron D Garcia, Vittoria A Smeglin, Francesca A Marino, Howard Eichenbaum
Recent studies have shown that hippocampal "time cells" code for sequential moments in temporally organized experiences. However, it is currently unknown whether these temporal firing patterns critically rely on upstream cortical input. Here we employ an optogenetic approach to explore the effect of large-scale inactivation of the medial entorhinal cortex on temporal, as well as spatial and object, coding by hippocampal CA1 neurons. Medial entorhinal inactivation produced a specific deficit in temporal coding in CA1 and resulted in significant impairment in memory across a temporal delay...
April 13, 2017: Neuron
https://www.readbyqxmd.com/read/28434399/the-next-generation-of-immunotherapy-keeping-lung-cancer-in-check
#15
REVIEW
Ashwin Somasundaram, Timothy F Burns
Lung cancer is the deadliest malignancy with more cancer deaths per year than the next three cancers combined. Despite remarkable advances in targeted therapy, advanced lung cancer patients have not experienced a significant improvement in mortality. Lung cancer has been shown to be immunogenic and responsive to checkpoint blockade therapy. Checkpoint signals such as CTLA-4 and PD-1/PD-L1 dampen T cell activation and allow tumors to escape the adaptive immune response. Response rates in patients with pretreated, advanced NSCLC were much higher and more durable with PD-1 blockade therapy compared to standard-of-care, cytotoxic chemotherapy...
April 24, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28432872/human-effector-memory-t-helper-cells-engage-with-mouse-macrophages-and-cause-graft-versus-host-like-pathology-in-skin-of-humanized-mice-used-in-a-nonclinical-immunization-study
#16
Bala S Sundarasetty, Valery Volk, Sebastian J Theobald, Susanne Rittinghausen, Dirk Schaudien, Vanessa Neuhaus, Constanca Figueiredo, Andreas Schneider, Laura Gerasch, Adele Mucci, Thomas Moritz, Constantin von Kaisenberg, Loukia M Spineli, Katherina Sewald, Armin Braun, Henning Weigt, Arnold Ganser, Renata Stripecke
Humanized mice engrafted with human hematopoietic stem cells and developing functional human T-cell adaptive responses are in critical demand to test human-specific therapeutics. We previously showed that humanized mice immunized with long-lived induced-dendritic cells loaded with the pp65 viral antigen (iDCpp65) exhibited a faster development and maturation of T cells. Herein, we evaluated these effects in a long-term (36 weeks) nonclinical model using two stem cell donors to assess efficacy and safety. Relative to baseline, iDCpp65 immunization boosted the output of effector memory CD4(+) T cells in peripheral blood and lymph nodes...
April 19, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28432326/a-novel-mechanism-linking-memory-stem-cells-with-innate-immunity-in-protection-against-hiv-1-infection
#17
Yufei Wang, Trevor Whittall, Stuart Neil, Gary Britton, Mukesh Mistry, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Jaranit Kaewkungwal, Sorachai Nitayaphan, Xuesong Yu, Alicia Sato, Robert J O'Connell, Nelson L Michael, Merlin L Robb, Jerome H Kim, Thomas Lehner
HIV infection affects 37 million people and about 1.7 million are infected annually. Among the phase III clinical trials only the RV144 vaccine trial elicited significant protection against HIV-1 acquisition, but the efficacy and immune memory were inadequate. To boost these vaccine functions we studied T stem cell memory (TSCM) and innate immunity. TSCM cells were identified by phenotypic markers of CD4(+) T cells and they were further characterised into 4 subsets. These expressed the common IL-2/IL-15 receptors and another subset of APOBEC3G anti-viral restriction factors, both of which were upregulated...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432133/do-memory-cd4-t-cells-keep-their-cell-type-programming-plasticity-versus-fate-commitment-t-cell-heterogeneity-plasticity-and-selection-in-humans
#18
Federica Sallusto, Antonino Cassotta, Daniel Hoces, Mathilde Foglierini, Antonio Lanzavecchia
The wide range of effector and memory T cells is instrumental for immune regulation and tailored mechanisms of protection against pathogens. Here, we will focus on human CD4 T cells and discuss T-cell plasticity and intraclonal diversification in the context of a progressive and selective model of CD4 T-cell differentiation.
April 21, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28432132/do-memory-cd4-t-cells-keep-their-cell-type-programming-plasticity-versus-fate-commitment-epigenome-a-dynamic-vehicle-for-transmitting-and-recording-cytokine-signaling
#19
John L Johnson, Golnaz Vahedi
CD4(+) T cells are critical for the elimination of an immense array of microbial pathogens. Although there are aspects of helper T-cell differentiation that can be modeled as a classic cell-fate commitment, CD4(+) T cells also maintain considerable flexibility in their transcriptional program. Here, we present an overview of chromatin biology during cellular reprogramming and, within this context, envision how the scope of cellular reprogramming may be expanded to further our understanding of the controversy surrounding CD4(+) T lymphocyte plasticity or determinism...
April 21, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28432129/do-memory-cd4-t-cells-keep-their-cell-type-programming-plasticity-versus-fate-commitment-complexities-of-interpretation-due-to-the-heterogeneity-of-memory-cd4-t-cells-including-t-follicular-helper-cells
#20
Shane Crotty
Plasticity is the ability of a cell type to convert to another cell type. There are multiple effector CD4 T-cell subtypes, including TH1, TH2, TH17, TH1*, CD4 CTL, TH9, and TFH cells. It is commonly thought that a CD4 T cell can readily show full plasticity-full conversion from one differentiated cell-and this propensity to plasticity is possessed by memory CD4 T cells. However, there remains no direct demonstration of in vivo-generated resting memory CD4 T-cell conversion to a different subtype on secondary antigen challenge in vivo in an intact animal at the single-cell level...
April 21, 2017: Cold Spring Harbor Perspectives in Biology
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