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immune reconstitution

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https://www.readbyqxmd.com/read/28749311/reconstitution-of-the-peripheral-immune-repertoire-following-withdrawal-of-fingolimod
#1
Mahtab Ghadiri, Leslie Fitz-Gerald, Ayman Rezk, Rui Li, Mukanthu Nyirenda, David Haegert, Paul Steven Giacomini, Amit Bar-Or, Jack Antel
BACKGROUND: Following fingolimod cessation, immune reconstitution or lack thereof may have consequences for disease rebound or safety of commencing alternative therapies. OBJECTIVE: To examine the degree and profile of peripheral blood lymphocyte reconstitution following fingolimod withdrawal. METHODS: Total lymphocyte counts (TLC) and CD4+/CD8+ T-cell counts were measured in 18 multiple sclerosis (MS) patients pre-treatment, on fingolimod, and up to 8-9 months post-cessation...
August 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28749310/reconstitution-of-the-peripheral-immune-repertoire-following-withdrawal-of-fingolimod
#2
Clemens Warnke, Jonas Graf, Hans-Peter Hartung
No abstract text is available yet for this article.
August 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28747447/long-term-aids-related-pcnsl-outcomes-with-hd-mtx-and-combined-antiretroviral-therapy
#3
Antoine Moulignier, Cédric Lamirel, Hervé Picard, Marie-Gisèle Lebrette, Corinne Amiel, Mohammed Hamidi, Marc Polivka, Jacqueline Mikol, Isabelle Cochereau, Gilles Pialoux
OBJECTIVE: To assess the characteristics and outcomes of patients with AIDS-related primary CNS lymphoma (AR-PCNSL) in the combined antiretroviral therapy (cART) era systematically treated with high-dose methotrexate (HD-MTX). METHODS: We retrospectively analyzed (intention-to-treat analysis) 51 consecutive patients with AR-PCNSL (median age 39 years) who were diagnosed from 1996 to 2014 and treated with a median of 6 (range 1-15) infusions of HD-MTX (3 g/m(2)) combined with cART...
July 26, 2017: Neurology
https://www.readbyqxmd.com/read/28746819/humanized-mouse-models-for-human-immunodeficiency-virus-infection
#4
Matthew D Marsden, Jerome A Zack
Human immunodeficiency virus (HIV) remains a significant source of morbidity and mortality worldwide. No effective vaccine is available to prevent HIV transmission, and although antiretroviral therapy can prevent disease progression, it does not cure HIV infection. Substantial effort is therefore currently directed toward basic research on HIV pathogenesis and persistence and developing methods to stop the spread of the HIV epidemic and cure those individuals already infected with HIV. Humanized mice are versatile tools for the study ofHIVand its interaction with the human immune system...
July 26, 2017: Annual Review of Virology
https://www.readbyqxmd.com/read/28737510/lymphocytes-transiently-expressing-virus-specific-t-cell-receptors-reduce-hepatitis-b-virus-infection
#5
Janine Kah, Sarene Koh, Tassilo Volz, Erica Ceccarello, Lena Allweiss, Marc Lütgehetmann, Antonio Bertoletti, Maura Dandri
Adoptive transfer of T cells engineered to express a hepatitis B virus-specific (HBV-specific) T cell receptor (TCR) may supplement HBV-specific immune responses in chronic HBV patients and facilitate HBV control. However, the risk of triggering unrestrained proliferation of permanently engineered T cells raises safety concerns that have hampered testing of this approach in patients. The aim of the present study was to generate T cells that transiently express HBV-specific TCRs using mRNA electroporation and to assess their antiviral and pathogenetic activity in vitro and in HBV-infected human liver chimeric mice...
July 24, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28736762/confusion-in-the-study-of-immune-reconstitution-inflammatory-syndrome
#6
Claudia Alvarado-de la Barrera, Gustavo Reyes-Terán
As a consequence of late presentation for HIV care, a significant proportion of individuals develop immune reconstitution inflammatory syndrome (IRIS) soon after initiation of antiretroviral therapy. Incidence, predictors, and models of pathogenesis of IRIS vary in the literature. Here we discuss factors that may contribute to this lack of consensus. We propose that different pathogens drive different types of IRIS and suggest that these clinical conditions should be studied individually and not grouped under the general heading of "IRIS...
2017: Pathogens & Immunity
https://www.readbyqxmd.com/read/28733349/constitutive-ido1-expression-in-human-tumors-is-driven-by-cyclooxygenase-2-and-mediates-intrinsic-immune-resistance
#7
Marc Hennequart, Luc Pilotte, Stefania Cane, Delia Hoffmann, Vincent Stroobant, Etienne De Plaen, Benoît J Van den Eynde
Tumors use various mechanisms to avoid immune destruction. Cyclooxygenase-2 (COX-2) expression may be a driver of immune suppression in melanoma, but the mechanisms involved remain elusive. Here, we show that COX-2 expression drives constitutive expression of indoleamine 2,3-dioxygenase 1 (IDO1) in human tumor cells. IDO1 is an immunosuppressive enzyme that degrades tryptophan. In a series of seven human tumor lines, constitutive IDO1 expression depends on COX-2 and prostaglandin E2 (PGE2), which, upon autocrine signaling through the EP receptor, activates IDO1 via the PKC and PI3K pathways...
July 21, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28732079/lmp1-mediated-glycolysis-induces-myeloid-derived-suppressor-cell-expansion-in-nasopharyngeal-carcinoma
#8
Ting-Ting Cai, Shu-Biao Ye, Yi-Na Liu, Jia He, Qiu-Yan Chen, Hai-Qiang Mai, Chuan-Xia Zhang, Jun Cui, Xiao-Shi Zhang, Pierre Busson, Yi-Xin Zeng, Jiang Li
Myeloid-derived suppressor cells (MDSCs) are expanded in tumor microenvironments, including that of Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC). The link between MDSC expansion and EBV infection in NPC is unclear. Here, we show that EBV latent membrane protein 1 (LMP1) promotes MDSC expansion in the tumor microenvironment by promoting extra-mitochondrial glycolysis in malignant cells, which is a scenario for immune escape initially suggested by the frequent, concomitant detection of abundant LMP1, glucose transporter 1 (GLUT1) and CD33+ MDSCs in tumor sections...
July 21, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28731329/generation-and-characterization-of-anti-vglut-nanobodies-acting-as-inhibitors-of-transport
#9
Stephan Schenck, Laura Kunz, Daniela Sahlender, Els Pardon, Eric R Geertsma, Iaroslav Savtchouk, Toshiharu Suzuki, Yvonne Neldner, Saša Štefanić, Jan Steyaert, Andrea Volterra, Raimund Dutzler
The uptake of glutamate by synaptic vesicles is mediated by vesicular glutamate transporters (VGLUTs). The central role of these transporters in excitatory neurotransmission underpins their importance as pharmacological targets. Although several compounds inhibit VGLUTs, highly specific inhibitors were so far unavailable, thus limiting applications to in vitro experiments. Besides their potential in pharmacology, specific inhibitors would also be beneficial for the elucidation of transport mechanisms. To overcome this shortage, we generated nanobodies (Nbs) by immunization of a llama with purified rat VGLUT1 and subsequent selection of binders from a phage display library...
July 21, 2017: Biochemistry
https://www.readbyqxmd.com/read/28729150/impact-of-dendritic-cell-recovery-on-outcomes-after-umbilical-cord-blood-and-sibling-donor-transplantation-for-hematologic-malignancies
#10
Waseem Touma, Claudio G Brunstein, Michael R Verneris, Qing Cao, Julie Curtsinger, Jeffrey S Miller, Veronika Bachanova
Dendritic cells (DCs) orchestrate immune responses after allogeneic hematopoietic cell transplantation (HCT). We studied the association of donor myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) recovery in the landmark analysis of umbilical cord blood (UCB) and matched related donor (RD) HCT. Eighty patients (42 UCB and 38 RD recipients) with a day 100 (D+100) blood sample were included in the analysis. Median age was 51 years (20-71). Most patients had acute leukemia (50%) or lymphoma (23%) and received reduced-intensity conditioning (75%)...
July 17, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28723708/subclinical-herpesvirus-shedding-among-hiv-1-infected-men-on-antiretroviral-therapy
#11
Arcadio Agudelo-Hernandez, Yue Chen, Arlene Bullotta, William G Buchanan, Cynthia R Klamar-Blain, Luann Borowski, Sharon A Riddler, Charles R Rinaldo, Bernard Jc Macatangay
DESIGN: We evaluated the subclinical shedding of 6 different herpesviruses in antiretroviral drug-treated HIV(+) men who have sex with men (MSM), and determined how this is associated with markers of inflammation and immune activation. METHODS: We obtained blood, semen, throat washing, urine, and stool from 15 antiretroviral-treated HIV-1-infected MSM with CD4 T cell reconstitution, and 12 age-matched HIV(-) MSM from the Multicenter AIDS Cohort Study at 4 timepoints over 24 weeks to measure DNA levels of cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus 1 and 2, human herpesvirus 6 (HHV6), and HHV8...
July 18, 2017: AIDS
https://www.readbyqxmd.com/read/28722160/placental-proteomics-reveal-insights-into-fetal-alcohol-spectrum-disorders
#12
Katie L Davis-Anderson, Sebastian Berger, Emilie R Lunde-Young, Vishal D Naik, Heewon Seo, Greg A Johnson, Hanno Steen, Jayanth Ramadoss
Fetal alcohol spectrum disorders (FASD) describe many of the well-known neurodevelopmental deficits afflicting children exposed to alcohol in utero. The effects of alcohol on the maternal-fetal interface, especially the placenta, have been less explored. We herein hypothesized that chronic binge alcohol exposure during pregnancy significantly alters the placental protein profile in a rat FASD model METHODS: Pregnant rats were orogastrically treated daily with alcohol (4.5 g/kg, gestational day (GD) 5-10; 6...
July 19, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28720717/sting-is-an-essential-mediator-of-the-ku70-mediated-production-of-ifn-%C3%AE-1-in-response-to-exogenous-dna
#13
Hongyan Sui, Ming Zhou, Hiromi Imamichi, Xiaoli Jiao, Brad T Sherman, H Clifford Lane, Tomozumi Imamichi
We previously identified Ku70, a subunit of a DNA repair protein complex, as a cytosolic DNA sensor that induces the production of interferon-λ1 (IFN-λ1) by human primary cells and cell lines. IFN-λ1 is a type III IFN and has similar antiviral activity to that of the type I IFNs (IFN-α and IFN-β). We observed that human embryonic kidney (HEK) 293T cells, which are deficient in the innate immune adaptor protein STING (stimulator of IFN genes), did not produce IFN-λ1 in response to DNA unless they were reconstituted with STING...
July 18, 2017: Science Signaling
https://www.readbyqxmd.com/read/28720549/evolutionary-basis-of-a-new-approach-for-the-treatment-of-malignant-brain-tumors-from-mice-to-humans
#14
Pedro R Lowenstein, Maria G Castro
Glioma cells are one of the most aggressive and malignant tumors. Following initial surgery, and radio-chemotherapy they progress rapidly, so that patients' median survival remains under two years. They invade throughout the brain, which makes them difficult to treat, and are universally lethal. Though total resection is always attempted it is not curative. Standard of care in 2016 comprises surgical resection, radiotherapy and chemotherapy (temozolomide). Median survival is currently ~14-20months post-diagnosis though it can be higher in high complexity medical university centers, or during clinical trials...
July 15, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28717041/activation-of-sting-in-hepatocytes-suppresses-the-replication-of-hepatitis-b-virus
#15
Fang Guo, Liudi Tang, Sainan Shu, Mohit Sehgal, Muhammad Sheraz, Bowei Liu, Qiong Zhao, Junjun Cheng, Xuesen Zhao, Tianlun Zhou, Jinhong Chang, Ju-Tao Guo
Induction of interferon and proinflammatory cytokines is a hallmark of the infection of many different viruses. However, hepatitis B virus (HBV) does not elicit a detectable cytokine response in infected hepatocytes. In order to investigate the molecular mechanism underlying the innate immune evasion, a functional cGAS-STING pathway was reconstituted in a human hepatoma cell line supporting tetracycline-inducible HBV replication. It was demonstrated that induction of HBV replication neither activated nor inhibited this cytosolic DNA sensing pathway...
July 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28716863/opposing-regulation-and-roles-for-phd3-in-lung-dendritic-cells-and-alveolar-macrophages
#16
Simon J Tavernier, Nele Vanlangenakker, Jessica Vetters, Peter Carmeliet, Sophie Janssens, Bart N Lambrecht
The prolyl hydroxylase domain-containing enzymes (PHDs) are important metabolic sensors of the cell and its environment, which might be employed to alert cells of the immune system. These enzymes regulate the expression of the hypoxia inducible factor (HIF) isoforms and NF-κB, crucial transcription factors controlling cellular metabolism and inflammation. PHD/HIF signaling is activated in the allergic lung and is proposed as a potential druggable pathway. Here, we investigated the regulation and role of the PHD isoforms in CD11c-expressing dendritic cells (DCs) and macrophages (Mϕ), sensors of the environment and crucial antigen-presenting cells in the pathogenesis of asthma...
July 17, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28716805/sensing-of-viral-and-endogenous-rna-by-zbp1-dai-induces-necroptosis
#17
Jonathan Maelfait, Layal Liverpool, Anne Bridgeman, Katherine B Ragan, Jason W Upton, Jan Rehwinkel
Nucleic acids are potent triggers for innate immunity. Double-stranded DNA and RNA adopt different helical conformations, including the unusual Z-conformation. Z-DNA/RNA is recognised by Z-binding domains (ZBDs), which are present in proteins implicated in antiviral immunity. These include ZBP1 (also known as DAI or DLM-1), which induces necroptosis, an inflammatory form of cell death. Using reconstitution and knock-in models, we report that mutation of key amino acids involved in Z-DNA/RNA binding in ZBP1's ZBDs prevented necroptosis upon infection with mouse cytomegalovirus...
July 17, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28713662/subacute-sclerosing-panencephalitis-in-a-child-suffering-from-human-immunodeficiency-virus-on-highly-active-antiretroviral-therapy-can-this-be-another-instance-of-immune-reconstitution-inflammatory-syndrome
#18
Ashutosh Gupta, Suman Kushwaha, Mushbiq Manzoor, Shah Faisal Ahmad Tarfarosh
We report a 12-year-old boy with human immunodeficiency virus (HIV) who presented with rapidly progressive difficulty in ambulation. The symptoms started to worsen when he was put on antiretroviral therapy (ART). Our findings show that the dynamics of HIV-related immune suppression and highly active antiretroviral therapy (HAART) have an impact on the clinical course of Subacute sclerosing panencephalitis (SSPE). Slow progression is expected in children on HAART but in our case, we observe a complex interaction of the virus with the immune system and modification of disease course of SSPE with ART...
June 13, 2017: Curēus
https://www.readbyqxmd.com/read/28713390/hematopoietic-stem-cell-transplantation-in-an-infant-with-immunodeficiency-centromeric-instability-and-facial-anomaly-syndrome
#19
Katharina L Gössling, Cyrill Schipp, Ute Fischer, Florian Babor, Gerhard Koch, Friedhelm R Schuster, Jutta Dietzel-Dahmen, Dagmar Wieczorek, Arndt Borkhardt, Roland Meisel, Michaela Kuhlen
Immunodeficiency, centromeric instability, and facial anomaly (ICF) syndrome is a rare autosomal recessive genetic condition with severe immunodeficiency, which leads to lethal infections if not recognized and treated in early childhood. Up-to-date treatment regimens consist of prophylactic and supportive treatment of the recurrent infections. Here, we report the case of a 1-year-old boy of Moroccan consanguineous parents, who was diagnosed at 4 months of age with ICF syndrome with a homozygous missense mutation in the DNMT3B gene...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28704654/persistent-kshv-infection-increases-ebv-associated-tumor-formation-in%C3%A2-vivo-via-enhanced-ebv-lytic-gene-expression
#20
Donal McHugh, Nicole Caduff, Mario Henrique M Barros, Patrick C Rämer, Ana Raykova, Anita Murer, Vanessa Landtwing, Isaak Quast, Christine T Styles, Michael Spohn, Adeola Fowotade, Henri-Jacques Delecluse, Alexandra Papoudou-Bai, Yong-Moon Lee, Jin-Man Kim, Jaap Middeldorp, Thomas F Schulz, Ethel Cesarman, Andrea Zbinden, Riccarda Capaul, Robert E White, Martin J Allday, Gerald Niedobitek, David J Blackbourn, Adam Grundhoff, Christian Münz
The human tumor viruses Epstein-Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV) establish persistent infections in B cells. KSHV is linked to primary effusion lymphoma (PEL), and 90% of PELs also contain EBV. Studies on persistent KSHV infection in vivo and the role of EBV co-infection in PEL development have been hampered by the absence of small animal models. We developed mice reconstituted with human immune system components as a model for KSHV infection and find that EBV/KSHV dual infection enhanced KSHV persistence and tumorigenesis...
July 12, 2017: Cell Host & Microbe
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