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T cell memory

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https://www.readbyqxmd.com/read/28724365/leflunomide-is-equally-efficacious-and-safe-compared-to-low-dose-rituximab-in-refractory-rheumatoid-arthritis-given-in-combination-with-methotrexate-results-from-a-randomized-double-blind-controlled-clinical-trial
#1
Harindu Wijesinghe, Priyadharshini Galappatthy, Rajiva de Silva, Suranjith L Seneviratne, Ushagowry Saravanamuttu, Preethi Udagama, Melanie Hart, Peter Kelleher, Upul Senerath, Rohini Fernandopulle, Lilani P Weerasekera, Lalith S Wijayaratne
BACKGROUND: The standard dose of rituximab used in rheumatoid arthritis (RA) is 1000 mg but recent studies have shown that low dose (500 mg) is also effective. Efficacy of low dose rituximab in rheumatoid arthritis (RA) refractory to first-line non-biologic Disease Modifying Anti Rheumatic Drugs (DMARDs), compared to leflunomide is unknown. In a tertiary care referral setting, we conducted a randomized, double blind controlled clinical trial comparing the efficacy and safety of low-dose rituximab-methotrexate combination with leflunomide-methotrexate combination...
July 19, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/28723914/safety-and-pharmacodynamics-of-dalazatide-a-kv1-3-channel-inhibitor-in-the-treatment-of-plaque-psoriasis-a-randomized-phase-1b-trial
#2
Eric J Tarcha, Chelsea M Olsen, Peter Probst, David Peckham, Ernesto J Muñoz-Elías, James G Kruger, Shawn P Iadonato
BACKGROUND: Dalazatide is a specific inhibitor of the Kv1.3 potassium channel. The expression and function of Kv1.3 channels are required for the function of chronically activated memory T cells, which have been shown to be key mediators of autoimmune diseases, including psoriasis. OBJECTIVE: The primary objective was to evaluate the safety of repeat doses of dalazatide in adult patients with mild-to-moderate plaque psoriasis. Secondary objectives were to evaluate clinical proof of concept and the effects of dalazatide on mediators of inflammation in the blood and on chronically activated memory T cell populations...
2017: PloS One
https://www.readbyqxmd.com/read/28723667/resistance-to-ctla-4-checkpoint-inhibition-reversed-through-selective-elimination-of-granulocytic-myeloid-cells
#3
Paul E Clavijo, Ellen C Moore, Jianhong Chen, Ruth J Davis, Jay Friedman, Young Kim, Carter Van Waes, Zhong Chen, Clint T Allen
PURPOSE: Local immunosuppression remains a critical problem that limits clinically meaningful response to checkpoint inhibition in patients with head and neck cancer. Here, we assessed the impact of MDSC elimination on responses to CTLA-4 checkpoint inhibition. EXPERIMENTAL DESIGN: Murine syngeneic carcinoma immune infiltrates were characterized by flow cytometry. Granulocytic MDSCs (gMDSCs) were depleted and T-lymphocyte antigen-specific responses were measured...
June 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28722019/sustained-accumulation-of-antigen-presenting-cells-after-infection-promotes-local-t-cell-immunity
#4
Nicholas Collins, Katharina Hochheiser, Francis R Carbone, Thomas Gebhardt
Antigen-presenting cells (APC) such as dendritic cells (DC) and macrophages are critical for T cell-mediated immunity. While it is established that memory T cells accumulate and persist in peripheral tissues after the resolution of infection, whether this is also the case for APC remains unclear. Here, we report that CCR2-dependent cells infiltrate skin during acute infection with herpes simplex virus (HSV)-1 and subsequently give rise to localized populations of dendritic cells and macrophages. These APC are found at elevated numbers at sites of resolved infection or inflammation compared to unaffected regions of skin...
July 19, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28722017/the-role-of-age-related-t-cell-differentiation-in-patients-with-renal-replacement-therapy
#5
Matthias Schaier, Angele Leick, Lorenz Uhlmann, Florian Kälble, Volker Eckstein, Anthony Ho, Stefan Meuer, Karsten Mahnke, Claudia Sommerer, Martin Zeier, Andrea Steinborn
Dialysis patients have deficiencies regarding the generation of immune responses and show an increased susceptibility for infections. Persisting uremic conditions are made responsible for the increased aging of their immune system. In this study, we analyzed whether age-related differences in the differentiation of both recent-thymic-emigrant-(RTE)-regulatory (Tregs) and RTE-responder T cells (Tresps) into CD31(-)-memory Tregs/Tresps led to differences in the suppressive activity of naïve and memory Tregs on autologous Tresps between healthy volunteers and dialysis patients...
July 19, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28720549/evolutionary-basis-of-a-new-approach-for-the-treatment-of-malignant-brain-tumors-from-mice-to-humans
#6
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/28720467/intradermal-immunization-with-raav1-vector-induces-robust-memory-cd8-t-cell-responses-independently-of-transgene-expression-in-dcs
#7
Alexandre Ghenassia, David-Alexandre Gross, Stéphanie Lorain, Fabiola Tros, Dominique Urbain, Sofia Benkhelifa-Ziyyat, Alain Charbit, Jean Davoust, Pascal Chappert
Recombinant adeno-associated viral (rAAV) vectors exhibit interesting properties as vaccine carriers for their ability to induce long-lasting antibody responses. However, rAAV-based vaccines have been suggested to trigger functionally impaired long-term memory CD8(+) T cell responses, in part due to poor dendritic cell (DC) transduction. Such results, albeit limited to intramuscular immunization, undermined the use of rAAV as vaccine vehicles against intracellular pathogens. We report here that intradermal immunization with a model rAAV2/1-based vaccine drives the development of bona fide long-term memory CD8(+) T cell responses...
July 15, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28720421/assessment-of-the-hiv-1-reservoir-in-cd4-regulatory-t-cells-by-a-droplet-digital-pcr-based-approach
#8
Gábor Artúr Dunay, Anastasia Solomatina, Silke Kummer, Anja Hüfner, Julia Katharina Bialek, Johanna Maria Eberhard, Eva Tolosa, Joachim Hauber, Julian Schulze Zur Wiesch
The relative contribution of regulatory T cells (Treg) as reservoir of HIV-1 in patients on chronic antiretroviral therapy is unclear to date. The aim of the current study was to assess the total HIV DNA burden and replication competent viral reservoir in Treg in comparison to central and effector memory cells (Tcm and Tem). Peripheral blood mononuclear cells were obtained from 10 HIV patients treated with antiretroviral therapy and one HIV elite controller. Droplet Digital PCR (ddPCR) was used to quantify total HIV DNA loads in FACS sorted CD4+ Treg (CD25+CD127lo) as compared with Tcm (CD45RO+CCR7+) and Tem (CD45RO+CCR7-)...
July 15, 2017: Virus Research
https://www.readbyqxmd.com/read/28719821/bcg-old-workhorse-new-skills
#9
REVIEW
M Gengenbacher, N E Nieuwenhuizen, She Kaufmann
Bacille Calmette-Guérin (BCG), the only tuberculosis (TB) vaccine in clinical practice, has limitations in efficacy, immunogenicity and safety. Much current TB vaccine research focuses on engineering live mycobacteria to interfere with phagosome biology and host intracellular pathways including apoptosis and autophagy, with candidates such as BCG Δzmp1, BCG ΔureC::hly, BCG::ESX-1(Mmar), Mtb ΔphoP ΔfadD26, Mtb ΔRD1 ΔpanCD and M. smegmatis Δesx-3::esx-3(Mtb) in the development pipeline. Correlates of protection in preclinical studies include increased central memory CD4(+) T cells and recruitment of antigen-specific T cells to the lungs, with mucosal vaccination found to be superior to parenteral vaccination...
July 15, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28719652/long-term-follow-up-of-human-t-cell-responses-to-conserved-hiv-1-regions-elicited-by-dna-simian-adenovirus-mva-vaccine-regimens
#10
Nathifa Moyo, Nicola J Borthwick, Edmund G Wee, Silvia Capucci, Alison Crook, Lucy Dorrell, Tomáš Hanke
BACKGROUND: Durability of vaccine-elicited immune responses is one of the key determinants for vaccine success. Our aim is to develop a vaccination strategy against the human immunodeficiency virus type 1 (HIV-1), which induces protective and durable CD8+ T-cell responses. The central theorem of our approach is to focus T cells on highly conserved regions of the HIV-1 proteome and this is achieved through the use of the first-generation conserved vaccine immunogen HIVconsv. This immunogen vectored by plasmid DNA, simian adenovirus and poxvirus MVA was tested in healthy, HIV-1-negative adults in UK and induced high magnitudes of HIVconsv-specific plurifunctional CD8+ T cells capable of in vitro HIV-1 inhibition...
2017: PloS One
https://www.readbyqxmd.com/read/28718002/infectious-pathogens-may-trigger-specific-allo-hla-reactivity-via-multiple-mechanisms
#11
REVIEW
Lloyd D'Orsogna, Heleen van den Heuvel, Cees van Kooten, Sebastiaan Heidt, Frans H J Claas
Transplant recipients can be sensitized against allo-HLA antigens by previous transplantation, blood transfusion, or pregnancy. While there is growing awareness that multiple components of the immune system can act as effectors of the alloresponse, the role of infectious pathogen exposure in triggering sensitization and allograft rejection has remained a matter of much debate. Here, we describe that exposure to pathogens may enhance the immune response to allogeneic HLA antigens via different pathways. The potential role of allo-HLA cross-reactivity of virus-specific memory T cells, activation of innate immunity leading to a more efficient induction of the adaptive alloimmune response by antigen-presenting cells, and bystander activation of existing memory B cell activation will be discussed in this review...
July 17, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28716826/il-10-producing-infliximab-specific-t-cells-regulate-the-antidrug-t-cell-response-in-exposed-patients
#12
Alessandra Vultaggio, Francesca Nencini, Sara Pratesi, Daniele Cammelli, Maria Totaro, Sergio Romagnani, Enrico Maggi, Andrea Matucci
Infliximab (IFX) is a chimeric mAb that can lead to the appearance of anti-drug Abs. Recent research has identified the presence of circulating IFX-specific T cells in treated patients. The aim of the study was to analyze the functional characteristics of IFX-specific T cells, in particular their capability to produce biologically active regulatory cytokines. Drug-stimulated PBMCs or coculture systems were used to detect memory T cells in treated patients. The cytokines produced by IFX-specific T cells, T cell lines, and T cell clones were evaluated at the mRNA and protein levels...
July 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28716576/tlr9-mediated-conditioning-of-liver-environment-is-essential-for-successful-intrahepatic-immunotherapy-and-effective-memory-recall
#13
Marcin Cebula, Mathias Riehn, Upneet Hillebrand, Ramona F Kratzer, Florian Kreppel, Georgia Koutsoumpli, Toos Daemen, Hansjörg Hauser, Dagmar Wirth
Immune defense against hepatotropic viruses such as hepatitis B (HBV) and hepatitis C (HCV) poses a major challenge for therapeutic approaches. Intrahepatic cytotoxic CD8 T cells that are crucial for an immune response against these viruses often become exhausted resulting in chronic infection. We elucidated the T cell response upon therapeutic vaccination in inducible transgenic mouse models in which variable percentages of antigen-expressing hepatocytes can be adjusted, providing mosaic antigen distribution and reflecting the varying viral antigen loads observed in patients...
July 14, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28715973/the-molecular-basis-for-human-immunodeficiency-virus-latency
#14
Uri Mbonye, Jonathan Karn
Although potent combination antiretroviral therapy can effectively block viral replication in the host, human immunodeficiency virus (HIV) persists due to the existence of latent but replication-competent proviruses residing primarily in a very small population of resting memory CD4(+) T cells. Viral latency is established when the expression of the autoregulatory viral trans-activating factor Tat is reduced to subthreshold levels. The absence of Tat reduces HIV transcription and protein production to levels that make the host cell invisible to the immune system and refractory to antiretroviral treatment...
July 17, 2017: Annual Review of Virology
https://www.readbyqxmd.com/read/28714979/translation-is-actively-regulated-during-the-differentiation-of-cd8-effector-t-cells
#15
Koichi Araki, Masahiro Morita, Annelise G Bederman, Bogumila T Konieczny, Haydn T Kissick, Nahum Sonenberg, Rafi Ahmed
Translation is a critical process in protein synthesis, but translational regulation in antigen-specific T cells in vivo has not been well defined. Here we have characterized the translatome of virus-specific CD8(+) effector T cells (Teff cells) during acute infection of mice with lymphocytic choriomeningitis virus (LCMV). Antigen-specific T cells exerted dynamic translational control of gene expression that correlated with cell proliferation and stimulation via the T cell antigen receptor (TCR). The translation of mRNAs that encode translation machinery, including ribosomal proteins, was upregulated during the T cell clonal-expansion phase, followed by inhibition of the translation of those transcripts when the CD8(+) Teff cells stopped dividing just before the contraction phase...
July 17, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28714866/ibrutinib-treatment-improves-t-cell-number-and-function-in-cll-patients
#16
Meixiao Long, Kyle Beckwith, Priscilla Do, Bethany L Mundy, Amber Gordon, Amy M Lehman, Kami J Maddocks, Carolyn Cheney, Jeffrey A Jones, Joseph M Flynn, Leslie A Andritsos, Farrukh Awan, Joseph A Fraietta, Carl H June, Marcela V Maus, Jennifer A Woyach, Michael A Caligiuri, Amy J Johnson, Natarajan Muthusamy, John C Byrd
BACKGROUND: Ibrutinib has been shown to have immunomodulatory effects by inhibiting Bruton's tyrosine kinase (BTK) and IL-2-inducible T cell kinase (ITK). The relative importance of inhibiting these 2 kinases has not been examined despite its relevance to immune-based therapies. METHODS: Peripheral blood mononuclear cells from chronic lymphocytic leukemia (CLL) patients on clinical trials of ibrutinib (BTK/ITK inhibitor; n = 19) or acalabrutinib (selective BTK inhibitor; n = 13) were collected serially...
July 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28714465/enhanced-anti-tumour-immunity-requires-the-interplay-between-resident-and-circulating-memory-cd8-t-cells
#17
Michel Enamorado, Salvador Iborra, Elena Priego, Francisco J Cueto, Juan A Quintana, Sarai Martínez-Cano, Ernesto Mejías-Pérez, Mariano Esteban, Ignacio Melero, Andrés Hidalgo, David Sancho
The goal of successful anti-tumoural immunity is the development of long-term protective immunity to prevent relapse. Infiltration of tumours with CD8(+) T cells with a resident memory (Trm) phenotype correlates with improved survival. However, the interplay of circulating CD8(+) T cells and Trm cells remains poorly explored in tumour immunity. Using different vaccination strategies that fine-tune the generation of Trm cells or circulating memory T cells, here we show that, while both subsets are sufficient for anti-tumour immunity, the presence of Trm cells improves anti-tumour efficacy...
July 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28713424/prolonged-survival-of-subcutaneous-allogeneic-islet-graft-by-donor-chimerism-without-immunosuppressive-treatment
#18
Brend Ray-Sea Hsu, Shin-Huei Fu, Aline Yen Ling Wang
The aim of this study was to investigate whether tolerance-induced protection of islets in the renal subcapsular space can also prevent subcutaneous allogeneic islets from being rejected. We used bone marrow stem cells from C57BL/6 (H2(b)) mice to construct donor chimerism in conditioned diabetic BALB/c (H2(d)) mice and investigated the effect of donor chimerism on engraftment and survival of subcutaneously transplanted allogeneic islets in streptozotocin-induced diabetic mice. We also studied the anti-inflammatory effect of mesenchymal stem cell on islet engraftment...
2017: International Journal of Endocrinology
https://www.readbyqxmd.com/read/28713387/human-cd6-down-modulation-following-t-cell-activation-compromises-lymphocyte-survival-and-proliferative-responses
#19
Esther Carrasco, Cristina Escoda-Ferran, Núria Climent, Cristina Miró-Julià, Inês T Simões, Mario Martínez-Florensa, Adelaida Sarukhan, Esther Carreras, Francisco Lozano
Available evidence indicates that the CD6 lymphocyte surface receptor is involved in T-cell developmental and activation processes, by facilitating cell-to-cell adhesive contacts with antigen-presenting cells and likely modulating T-cell receptor (TCR) signaling. Here, we show that in vitro activation of human T cells under different TCR-ligation conditions leads to surface downregulation of CD6 expression. This phenomenon was (i) concomitant to increased levels of soluble CD6 (sCD6) in culture supernatants, (ii) partially reverted by protease inhibitors, (iii) not associated to CD6 mRNA down-regulation, and (iv) reversible by stimulus removal...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28713279/antiepileptogenic-and-neuroprotective-effects-of-pergularia-daemia-on-pilocarpine-model-of-epilepsy
#20
Antoine K Kandeda, Germain S Taiwe, Fleur C O Moto, Gwladys T Ngoupaye, Gisele C N Nkantchoua, Jacqueline S K Njapdounke, Jean P O Omam, Simon Pale, Nadege Kouemou, Elisabeth Ngo Bum
In this study, we investigated antiepileptogenic and neuroprotective effects of the aqueous extract of Pergularia daemia roots (PDR) using in vivo and in vitro experimental models. In in vivo studies, status epilepticus caused by pilocarpine injection triggers epileptogenesis which evolves during about 1-2 weeks. After 2 h of status epilepticus, mice were treated during the epileptogenesis period for 7 days with sodium valproate and vitamin C (standards which demonstrated to alter epileptogenesis), or Pergularia daemia...
2017: Frontiers in Pharmacology
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