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https://www.readbyqxmd.com/read/28550793/acute-gonadotropin-releasing-hormone-agonist-treatment-enhances-extinction-memory-in-male-rats
#1
L Y Maeng, M B Taha, K K Cover, S S Glynn, M Murillo, K Lebron-Milad, M R Milad
Leuprolide acetate (LEU), also known as Lupron, is commonly used to treat prostate cancer in men. As a gonadotropin-releasing hormone (GnRH) receptor agonist, it initially stimulates the release of gonadal hormones, testosterone (T) and estradiol. This surge eventually suppresses these hormones, preventing the further growth and spread of cancer cells. Individuals receiving this treatment often report anxiety and cognitive changes, but LEU's effects on the neural mechanisms that are involved in anxiety during the trajectory of treatment are not well known...
May 17, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28550202/antigen-specific-t-cell-analysis-reveals-that-active-immune-responses-to-%C3%AE-cell-antigens-are-focused-on-a-unique-set-of-epitopes
#2
Junbao Yang, Xiaomin Wen, Hengyu Xu, Nadia Torres-Chinn, Cate Speake, Carla J Greenbaum, Gerald T Nepom, William W Kwok
CD38 is an activation marker that is present on recently activated T cells, but absent on resting memory T cells. In this study, we show that CD45RO(+)CD38(+) β cell Ag-specific CD4(+) T cells were present at higher frequencies in type 1 diabetes subjects compared with those in healthy subjects. These results imply an ongoing β cell immunity years after onset of diabetes and suggest these activated T cells have an active role in the disease process. The Ag specificities of these activated T cells were determined by a novel CD154 T cell epitope mapping assay...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28550199/comprehensive-approach-for-identifying-the-t-cell-subset-origin-of-cd3-and-cd28-antibody-activated-chimeric-antigen-receptor-modified-t-cells
#3
Michael Schmueck-Henneresse, Bilal Omer, Thomas Shum, Haruko Tashiro, Maksim Mamonkin, Natalia Lapteva, Sandhya Sharma, Lisa Rollins, Gianpietro Dotti, Petra Reinke, Hans-Dieter Volk, Cliona M Rooney
The outcome of therapy with chimeric Ag receptor (CAR)-modified T cells is strongly influenced by the subset origin of the infused T cells. However, because polyclonally activated T cells acquire a largely CD45RO(+)CCR7(-) effector memory phenotype after expansion, regardless of subset origin, it is impossible to know which subsets contribute to the final T cell product. To determine the contribution of naive T cell, memory stem T cell, central memory T cell, effector memory T cell, and terminally differentiated effector T cell populations to the CD3 and CD28-activated CAR-modified T cells that we use for therapy, we followed the fate and function of individually sorted CAR-modified T cell subsets after activation with CD3 and CD28 Abs (CD3/28), transduction and culture alone, or after reconstitution into the relevant subset-depleted population...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28550044/t-cells-lacking-hdac11-have-increased-effector-functions-and-mediate-enhanced-alloreactivity-in-a-murine-model
#4
David M Woods, Karrune V Woan, Fengdong Cheng, Andressa L Sodré, Dapeng Wang, Yongxia Wu, Zi Wang, Jie Chen, John Powers, Javier Pinilla-Ibarz, Yu Yu, Ya Zhang, Xuefeng Wu, Xiaoyan Zheng, Jeffrey Weber, Wayne Hancock, Edward Seto, Alejandro Villagra, Xue-Zhong Yu, Eduardo M Sotomayor
Histone acetylation and the families of enzymes responsible for controlling these epigenetic marks have been implicated in regulating T-cell maturation and phenotype. Here, we demonstrate a previously undefined role of histone deacetylase 11 (HDAC11) in regulating T-cell effector functions. Using EGFP-HDAC11 transgenic reporter mice, we found that HDAC11 expression was lower in effector relative to naïve and central memory T-cell populations, and activation of resting T-cells resulted in its decreased expression...
May 26, 2017: Blood
https://www.readbyqxmd.com/read/28549586/critical-role-of-hla-dr%C3%AE-binding-peptides-peripheral-flanking-residues-in-fully-protective-malaria-vaccine-development
#5
César Reyes, Rocío Rojas-Luna, Jorge Aza-Conde, Luisa Tabares, Manuel A Patarroyo, Manuel E Patarroyo
A vaccine candidate component must fit perfectly into the antigen presenting HLA-DRβ* molecule's groove (or canonical nonapeptide) peptide binding region (PBR) during antigen presentation for proper presentation to the T-cell receptor (TCR), conforming a specific and stable macromolecular complex and induce an appropriate immune response. Antigen's peripheral flanking residues (PFR, positions (p) -p2 and p10) must thus establish strong interactions with the HLA-DRβ* - TCR complex. These amino acids (aa) have specific physico-chemical characteristics enabling differentiation between non-protective but antibody-inducer (NPAI), short-lived protection inducer (SLPI) and long-lasting protection inducer (LLPI) peptides when used as an antimalarial vaccine component...
May 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28546503/frontline-science-functionally-impaired-geriatric-car-t-cells-rescued-by-increased-%C3%AE-5%C3%AE-1-integrin-expression
#6
Prajna Guha, Marissa Cunetta, Ponnandai Somasundar, N Joseph Espat, Richard P Junghans, Steven C Katz
Chimeric antigen receptor expressing T cells (CAR-T) are a promising form of immunotherapy, but the influence of age-related immune changes on CAR-T production remains poorly understood. We showed that CAR-T cells from geriatric donors (gCAR-T) are functionally impaired relative to CAR-T from younger donors (yCAR-T). Higher transduction efficiencies and improved cell expansion were observed in yCAR-T cells compared with gCAR-T. yCAR-T demonstrated significantly increased levels of proliferation and signaling activation of phosphorylated (p)Erk, pAkt, pStat3, and pStat5...
May 25, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28542595/antifungal-tc17-cells-are-durable-and-stable-persisting-as-long-lasting-vaccine-memory-without-plasticity-towards-ifn%C3%AE-cells
#7
Som Gowda Nanjappa, Andrew J McDermott, J Scott Fites, Kevin Galles, Marcel Wüthrich, George S Deepe, Bruce S Klein
Our understanding of persistence and plasticity of IL-17A+ memory T cells is clouded by conflicting results in models analyzing T helper 17 cells. We studied memory IL-17A+ CD8+ T-cell (Tc17) homeostasis, persistence and plasticity during fungal vaccine immunity. We report that vaccine-induced memory Tc17 cells persist with high fidelity to the type 17 phenotype. Tc17 cells persisted durably for a year as functional IL-17A+ memory cells without converting to IFNγ+ (Tc1) cells, although they produced multiple type I cytokines in the absence of residual vaccine antigen...
May 22, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28542586/antigen-delivery-to-dendritic-cells-shapes-human-cd4-and-cd8-t-cell-memory-responses-to-staphylococcus-aureus
#8
Julia Uebele, Christoph Stein, Minh-Thu Nguyen, Anja Schneider, Franziska Kleinert, Olga Tichá, Gabriele Bierbaum, Friedrich Götz, Isabelle Bekeredjian-Ding
Intracellular persistence of Staphylococcus aureus favors bacterial spread and chronic infections. Here, we provide evidence for the existence of human CD4+ and CD8+ T cell memory against staphylococcal antigens. Notably, the latter could provide a missing link in our understanding of immune control of intracellular S. aureus. The analyses showed that pulsing of monocyte-derived dendritic cells (MoDC) with native staphylococcal protein antigens induced release of Th2-associated cytokines and mediators linked to T regulatory cell development (G-CSF, IL-2 and IL-10) from both CD4+ and CD8+ T cells, thus revealing a state of tolerance predominantly arising from preformed memory T cells...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28540352/dataset-on-galanin-receptor-3-mutants-that-improve-recombinant-receptor-expression-and-stability-in-an-agonist-and-antagonist-bound-form
#9
Thao T Ho, Jasmine T Nguyen, Juping Liu, Pawel Stanczak, Aaron A Thompson, Yingzhuo G Yan, Jasmine Chen, Charles K Allerston, Charles L Dillard, Hao Xu, Nicholas J Shoger, Jill S Cameron, Mark E Massari, Kathleen Aertgeerts
Galanin Receptor 3 (GALR3) is a G-protein-coupled receptor with a widespread distribution in the brain and plays a role in a variety of physiologic processes including cognition/memory, sensory/pain processing, hormone secretion, and feeding behavior. Therefore, GALR3 is considered an attractive CNS drug target (Freimann et al., 2015) [1]. This dataset contains GALR3 point mutants that improve recombinant protein expression and thermal stability of the receptor contained in virus-like particles (VLPs) or obtained by detergent-purification of baculovirus-infected insect cells...
June 2017: Data in Brief
https://www.readbyqxmd.com/read/28539614/the-ccr5-antagonist-maraviroc-reverses-hiv-1-latency-in-vitro-alone-or-in-combination-with-the-pkc-agonist-bryostatin-1
#10
María Rosa López-Huertas, Laura Jiménez-Tormo, Nadia Madrid-Elena, Carolina Gutiérrez, Sara Rodríguez-Mora, Mayte Coiras, José Alcamí, Santiago Moreno
A potential strategy to cure HIV-1 infection is to use latency reversing agents (LRAs) to eliminate latent reservoirs established in resting CD4+ T (rCD4+) cells. As no drug has been shown to be completely effective, finding new drugs and combinations are of increasing importance. We studied the effect of Maraviroc (MVC), a CCR5 antagonist that activates NF-κB, on HIV-1 replication from latency. HIV-1-latency models based on CCL19 or IL7 treatment, before HIV-1 infection were used. Latently infected primary rCD4+ or central memory T cells were stimulated with MVC alone or in combination with Bryostatin-1, a PKC agonist known to reverse HIV-1 latency...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28539429/bolstering-the-number-and-function-of-hsv-1-specific-cd8-effector-memory-t-cells-and-tissue-resident-memory-t-cells-in-latently-infected-trigeminal-ganglia-reduces-recurrent-ocular-herpes-infection-and-disease
#11
Arif A Khan, Ruchi Srivastava, Aziz A Chentoufi, Elizabeth Kritzer, Sravya Chilukuri, Sumit Garg, David C Yu, Hawa Vahed, Lei Huang, Sabrina A Syed, Julie N Furness, Tien T Tran, Nesburn B Anthony, Christine E McLaren, John Sidney, Alessandro Sette, Randolph J Noelle, Lbachir BenMohamed
HSV type 1 (HSV-1) is a prevalent human pathogen that infects >3.72 billion individuals worldwide and can cause potentially blinding recurrent corneal herpetic disease. HSV-1 establishes latency within sensory neurons of trigeminal ganglia (TG), and TG-resident CD8(+) T cells play a critical role in preventing its reactivation. The repertoire, phenotype, and function of protective CD8(+) T cells are unknown. Bolstering the apparent feeble numbers of CD8(+) T cells in TG remains a challenge for immunotherapeutic strategies...
May 24, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28539278/-construction-of-specific-artificial-antigen-presenting-cells-for-in-vitro-activation-of-cd19-chimeric-antigen-receptor-t-cells
#12
Yao-Jun Peng, Qi-Yan Wu, Hong-Yu Liu, Jian Zhao, Hua-Feng Wei
OBJECTIVE: To construct CD19-specific artificial antigen-presenting cells (aAPCs) for in vitro activation and expansion of CD19 chimeric antigen receptor (CAR)-modified T cells (CD19-CAR-T) and investigate their cytotoxic effect. METHODS: CD19-specific aAPCs (NIH3T3-CD19/86, NIH3T3-CD19/86/137L) expressing costimulatory molecules CD86 and/or CD137L were prepared on the basis of NIH3T3 backbone cells by lentivirus-mediated gene transfer. Irradiated CD19-specific aAPCs were co-cultured with CD19-CAR-T cells to activate and amplify CD19-CAR-T cells...
May 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28537262/induction-of-resident-memory-t-cells-enhances-the-efficacy-of-cancer-vaccine
#13
Mevyn Nizard, Hélène Roussel, Mariana O Diniz, Soumaya Karaki, Thi Tran, Thibault Voron, Estelle Dransart, Federico Sandoval, Marc Riquet, Bastien Rance, Elie Marcheteau, Elizabeth Fabre, Marion Mandavit, Magali Terme, Charlotte Blanc, Jean-Baptiste Escudie, Laure Gibault, Françoise Le Pimpec Barthes, Clemence Granier, Luis C S Ferreira, Cecile Badoual, Ludger Johannes, Eric Tartour
Tissue-resident memory T cells (Trm) represent a new subset of long-lived memory T cells that remain in tissue and do not recirculate. Although they are considered as early immune effectors in infectious diseases, their role in cancer immunosurveillance remains unknown. In a preclinical model of head and neck cancer, we show that intranasal vaccination with a mucosal vector, the B subunit of Shiga toxin, induces local Trm and inhibits tumour growth. As Trm do not recirculate, we demonstrate their crucial role in the efficacy of cancer vaccine with parabiosis experiments...
May 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28537249/airway-t-cells-protect-against-rsv-infection-in-the-absence-of-antibody
#14
E Kinnear, L Lambert, J U McDonald, H M Cheeseman, L J Caproni, J S Tregoning
Tissue resident memory T (Trm) cells act as sentinels and early responders to infection. Respiratory syncytial virus (RSV)-specific Trm cells have been detected in the lungs after human RSV infection, but whether they have a protective role is unknown. To dissect the protective function of Trm cells, BALB/c mice were infected with RSV; infected mice developed antigen-specific CD8(+) Trm cells (CD103(+)/CD69(+)) in the lungs and airways. Intranasally transferring cells from the airways of previously infected animals to naïve animals reduced weight loss on infection in the recipient mice...
May 24, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28536578/expansion-of-cd25-negative-forkhead-box-p3-positive-t-cells-during-hiv-and-mycobacterium-tuberculosis-infection
#15
Matías T Angerami, Guadalupe V Suarez, María B Vecchione, Natalia Laufer, Diego Ameri, Graciela Ben, Hector Perez, Omar Sued, Horacio Salomón, María F Quiroga
Tuberculosis (TB) and HIV alter the immune system, and coinfected (HIV-TB) individuals usually present deregulations of T-lymphocytic immune response. We previously observed an increased frequency of "unconventional" CD4(+)CD25(-)FoxP3(+) Treg (uTreg) population during HIV-TB disease. Therefore, we aimed to explore the phenotype and function of uTreg and conventional CD4(+)CD25(+)FoxP3(+) Treg subsets (cTreg) in this context. We evaluated the expression of CD39, programmed cell death protein 1 (PD1), glucocorticoid-induced tumor necrosis factor receptor (GITR), and the effector/memory distribution by flow cytometry in cTreg and uTreg...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28536100/depletion-of-tumor-associated-macrophages-with-a-csf-1r-kinase-inhibitor-enhances-antitumor-immunity-and-survival-induced-by-dc-immunotherapy
#16
Floris Dammeijer, Lysanne A Lievense, Margaretha E H Kaijen-Lambers, Menno van Nimwegen, Koen Bezemer, Joost P Hegmans, Thorbald van Hall, Rudi W Hendriks, Joachim G Aerts
New immunotherapeutic strategies are needed to induce effective anti-tumor immunity in all cancer patients. Malignant mesothelioma is characterized by a poor prognosis and resistance to conventional therapies. Infiltration of tumor-associated macrophages (TAM) is prominent in mesothelioma and is linked to immune suppression, angiogenesis and tumor aggressiveness. Therefore, TAM depletion could potentially reactivate anti-tumor immunity. We show that M-CSFR-inhibition using the CSF-1R kinase inhibitor PLX3397 (pexidartinib) effectively reduced numbers of TAMs, circulating nonclassical monocytes, as well as amount of neo-angiogenesis and ascites in mesothelioma mouse models, but did not improve survival...
May 23, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28533941/changes-in-clinical-laboratory-parameters-and-pharmacodynamic-markers-in-response-to-blinatumomab-treatment-of-patients-with-relapsed-refractory-all
#17
Virginie Nägele, Andrea Kratzer, Gerhard Zugmaier, Chris Holland, Youssef Hijazi, Max S Topp, Nicola Gökbuget, Patrick A Baeuerle, Peter Kufer, Andreas Wolf, Matthias Klinger
BACKGROUND: Blinatumomab has shown a remission rate of 69% in an exploratory single-arm, phase II dose-escalation study in adult patients with relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL). We evaluated changes in laboratory parameters and immunopharmacodynamic markers in patients who received blinatumomab in the exploratory phase II study. METHODS: Data from 36 adults with relapsed/refractory ALL receiving blinatumomab as 4-week continuous IV infusions in various dose cohorts were analyzed for changes in liver enzymes, first-dose parameters, peripheral blood cell subpopulations, and cytokine/granzyme B release...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28533445/lung-cd4-tissue-resident-memory-t-cells-mediate-adaptive-immunity-induced-by-previous-infection-of-mice-with-bordetella-pertussis
#18
Mieszko M Wilk, Alicja Misiak, Róisín M McManus, Aideen C Allen, Marina A Lynch, Kingston H G Mills
Th1 and Th17 cells have an established role in protective immunity to Bordetella pertussis, but this evidence is based largely on peripheral T cells. There is emerging evidence that local tissue-resident memory T (TRM) cells that accumulate in tissue following mucosal infection may be crucial for long-term immunity. In this study, we examined the role of respiratory CD4 TRM cells in immunity to B. pertussis Natural immunity to B. pertussis induced by infection is considered long lasting and effective at preventing reinfection...
May 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28533414/manipulating-dna-damage-response-signaling-for-the-treatment-of-immune-mediated-diseases
#19
Jonathan P McNally, Scott H Millen, Vandana Chaturvedi, Nora Lakes, Catherine E Terrell, Eileen E Elfers, Kaitlin R Carroll, Simon P Hogan, Paul R Andreassen, Julie Kanter, Carl E Allen, Michael M Henry, Jay N Greenberg, Stephan Ladisch, Michelle L Hermiston, Michael Joyce, David A Hildeman, Jonathan D Katz, Michael B Jordan
Antigen-activated lymphocytes undergo extraordinarily rapid cell division in the course of immune responses. We hypothesized that this unique aspect of lymphocyte biology leads to unusual genomic stress in recently antigen-activated lymphocytes and that targeted manipulation of DNA damage-response (DDR) signaling pathways would allow for selective therapeutic targeting of pathological T cells in disease contexts. Consistent with these hypotheses, we found that activated mouse and human T cells display a pronounced DDR in vitro and in vivo...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28533093/safety-and-immunogenicity-of-a-live-attenuated-influenza-h5-candidate-vaccine-strain-a-17-turkey-turkey-05-133-h5n2-and-its-priming-effects-for-potential-pre-pandemic-use-a-randomised-double-blind-placebo-controlled-trial
#20
Punnee Pitisuttithum, Kobporn Boonnak, Supat Chamnanchanunt, Pilaipan Puthavathana, Viravarn Luvira, Hatairat Lerdsamran, Jaranit Kaewkungwal, Saranath Lawpoolsri, Vipa Thanachartwet, Udomsak Silachamroon, Wanibtisam Masamae, Alexandra Schuetz, Ponthip Wirachwong, Sit Thirapakpoomanunt, Larisa Rudenko, Erin Sparrow, Martin Friede, Marie-Paule Kieny
BACKGROUND: The emergence of highly pathogenic avian influenza H5N1 viruses has raised concerns about their pandemic potential. Vaccination is the most effective way of preventing influenza. In this study, we investigated the safety and immunogenicity of an avian H5N2 live attenuated influenza vaccine (LAIV H5N2) in healthy Thai adults and its priming immune responses with an H5N1 inactivated vaccine boost. METHODS: This study was done at the Vaccine Trial Centre at Mahidol University, Bangkok, Thailand and was divided into two parts...
May 19, 2017: Lancet Infectious Diseases
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