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Naïve T cells

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https://www.readbyqxmd.com/read/29472931/dendritic-cell-migration-to-skin-draining-lymph-nodes-is-controlled-by-dermatan-sulfate-and-determines-adaptive-immunity-magnitude
#1
Reza Nadafi, Jasper J Koning, Henrike Veninga, Xanthi N Stachtea, Tanja Konijn, Antonie Zwiers, Anders Malmström, Joke M M den Haan, Reina E Mebius, Marco Maccarana, Rogier M Reijmers
For full activation of naïve adaptive lymphocytes in skin-draining lymph nodes (LNs), presentation of peptide:MHC complexes by LN-resident and skin-derived dendritic cells (DCs) that encountered antigens (Ags) is an absolute prerequisite. To get to the nearest draining LN upon intradermal immunization, DCs need to migrate from the infection site to the afferent lymphatics, which can only be reached by traversing a collagen-dense network located in the dermis of the skin through the activity of proteolytic enzymes...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29472120/targeting-cd6-for-the-treatment-of-experimental-autoimmune-uveitis
#2
Lingjun Zhang, Yan Li, Wen Qiu, Brent A Bell, Nina Dvorina, William M Baldwin, Nora Singer, Timothy Kern, Rachel R Caspi, David A Fox, Feng Lin
OBJECTIVE: CD6 is emerging as a new target for treating many pathological conditions in which T cells are integrally involved, but even the latest data from studies of CD6 gene engineered mice were still contradictory. To address this issue, we studied experimental autoimmune uveitis (EAU), a model of autoimmune uveitis, in wild-type (WT) and CD6 knockout (KO) mice. METHODS: After EAU induction in WT and CD6 KO mice, we evaluated ocular inflammation and compared retinal antigen-specific T-cell responses using scanning laser ophthalmoscopy, spectral-domain optical coherence tomography, histopathology, and T cell recall assays...
February 19, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29471880/-18-f-fspg-pet-reveals-increased-cystine-glutamate-antiporter-xc-activity-in-a-mouse-model-of-multiple-sclerosis
#3
Aileen Hoehne, Michelle L James, Israt S Alam, John A Ronald, Bernadette Schneider, Aloma D'Souza, Timothy H Witney, Lauren E Andrews, Haley C Cropper, Deepak Behera, Gayatri Gowrishankar, Zhaoqing Ding, Tony Wyss-Coray, Frederick T Chin, Sandip Biswal, Sanjiv S Gambhir
BACKGROUND: The cystine/glutamate antiporter (xc-) has been implicated in several neurological disorders and, specifically, in multiple sclerosis (MS) as a mediator of glutamate excitotoxicity and proinflammatory immune responses. We aimed to evaluate an xc-specific positron emission tomography (PET) radiotracer, (4S)-4-(3-[18 F]fluoropropyl)-L-glutamate ([18 F]FSPG), for its ability to allow non-invasive monitoring of xc- activity in a mouse model of MS. METHODS: Experimental autoimmune encephalomyelitis (EAE) was induced in C57BL/6 mice by subcutaneous injection of myelin oligodendrocyte glycoprotein (MOG35-55 ) peptide in complete Freund's adjuvant (CFA) followed by pertussis toxin...
February 22, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29471332/mycobacterium-tuberculosis-infected-hematopoietic-stem-and-progenitor-cells-unable-to-express-inducible-nitric-oxide-synthase-propagate-tuberculosis-in-mice
#4
Stephen T Reece, Alexis Vogelzang, Julia Tornack, Wolfgang Bauer, Ulrike Zedler, Sandra Schommer-Leitner, Georg Stingl, Fritz Melchers, Stefan H E Kaufmann
Persistence of Mycobacterium tuberculosis within human bone marrow stem cells has been identified as a potential bacterial niche during latent tuberculosis. Using a murine model of tuberculosis, we show here that bone marrow stem and progenitor cells containing M. tuberculosis propagated tuberculosis when transferred to naive mice, given that both transferred cells and recipient mice were unable to express inducible nitric oxide synthase, which mediates killing of intracellular bacteria via nitric oxide. Our findings suggest that bone marrow stem and progenitor cells containing M...
February 17, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29470191/characterization-of-postinfusion-phenotypic-differences-in-fresh-versus-cryopreserved-tcr-engineered-adoptive-cell-therapy-products
#5
Theodore S Nowicki, Helena Escuin-Ordinas, Earl Avramis, Bartosz Chmielowski, Thinle Chodon, Beata Berent-Maoz, Xiaoyan Wang, Paula Kaplan-Lefko, Lili Yang, David Baltimore, James S Economou, Antoni Ribas, Begoña Comin-Anduix
Adoptive cell therapy (ACT) consisting of genetically engineered T cells expressing tumor antigen-specific T-cell receptors displays robust initial antitumor activity, followed by loss of T-cell activity/persistence and frequent disease relapse. We characterized baseline and longitudinal T-cell phenotype variations resulting from different manufacturing and administration protocols in patients who received ACT. Patients with melanoma who enrolled in the F5-MART-1 clinical trial (NCT00910650) received infusions of MART-1 T-cell receptors transgenic T cells with MART-1 peptide-pulsed dendritic cell vaccination...
February 21, 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29468144/vaccine-mediated-mechanisms-controlling-replication-of-francisella-tularensis-in-human-peripheral-blood-mononuclear-cells-using-a-co-culture-system
#6
Kjell Eneslätt, Igor Golovliov, Patrik Rydén, Anders Sjöstedt
Cell-mediated immunity (CMI) is normally required for efficient protection against intracellular infections, however, identification of correlates is challenging and they are generally lacking. Francisella tularensis is a highly virulent, facultative intracellular bacterium and CMI is critically required for protection against the pathogen, but how this is effectuated in humans is poorly understood. To understand the protective mechanisms, we established an in vitro co-culture assay to identify how control of infection of F...
2018: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29467758/predicting-early-viral-control-under-direct-acting-antiviral-therapy-for-chronic-hepatitis-c-virus-using-pretreatment-immunological-markers
#7
James A Hutchinson, Kilian Weigand, Akinbami Adenugba, Katharina Kronenberg, Jan Haarer, Florian Zeman, Paloma Riquelme, Matthias Hornung, Norbert Ahrens, Hans J Schlitt, Edward K Geissler, Jens M Werner
Recent introduction of all-oral direct-acting antiviral (DAA) treatment has revolutionized care of patients with chronic hepatitis C virus (HCV) infection. Regrettably, the high cost of DAA treatment is burdensome for healthcare systems and may be prohibitive for some patients who would otherwise benefit. Understanding how patient-related factors influence individual responses to DAA treatment may lead to more efficient prescribing. In this observational study, patients with chronic HCV infection were comprehensively monitored by flow cytometry to identify pretreatment immunological variables that predicted HCV RNA negativity within 4 weeks of commencing DAA treatment...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29467754/immune-repertoire-sequencing-using-molecular-identifiers-enables-accurate-clonality-discovery-and-clone-size-quantification
#8
Ke-Yue Ma, Chenfeng He, Ben S Wendel, Chad M Williams, Jun Xiao, Hui Yang, Ning Jiang
Unique molecular identifiers (MIDs) have been demonstrated to effectively improve immune repertoire sequencing (IR-seq) accuracy, especially to identify somatic hypermutations in antibody repertoire sequencing. However, evaluating the sensitivity to detect rare T cells and the degree of clonal expansion in IR-seq has been difficult due to the lack of knowledge of T cell receptor (TCR) RNA molecule copy number and a generalized approach to estimate T cell clone size from TCR RNA molecule quantification. This limited the application of TCR repertoire sequencing (TCR-seq) in clinical settings, such as detecting minimal residual disease in lymphoid malignancies after treatment, evaluating effectiveness of vaccination and assessing degree of infection...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29467329/t-cell-developmental-arrest-in-former-premature-infants-increases-risk-of-respiratory-morbidity-later-in-infancy
#9
Kristin M Scheible, Jason Emo, Nathan Laniewski, Andrea M Baran, Derick R Peterson, Jeanne Holden-Wiltse, Sanjukta Bandyopadhyay, Andrew G Straw, Heidie Huyck, John M Ashton, Kelly Schooping Tripi, Karan Arul, Elizabeth Werner, Tanya Scalise, Deanna Maffett, Mary Caserta, Rita M Ryan, Anne Marie Reynolds, Clement L Ren, David J Topham, Thomas J Mariani, Gloria S Pryhuber
The inverse relationship between gestational age at birth and postviral respiratory morbidity suggests that infants born preterm (PT) may miss a critical developmental window of T cell maturation. Despite a continued increase in younger PT survivors with respiratory complications, we have limited understanding of normal human fetal T cell maturation, how ex utero development in premature infants may interrupt normal T cell development, and whether T cell development has an effect on infant outcomes. In our longitudinal cohort of 157 infants born between 23 and 42 weeks of gestation, we identified differences in T cells present at birth that were dependent on gestational age and differences in postnatal T cell development that predicted respiratory outcome at 1 year of age...
February 22, 2018: JCI Insight
https://www.readbyqxmd.com/read/29466737/suppression-of-tcf1-by-inflammatory-cytokines-facilitates-effector-cd8-t-cell-differentiation
#10
Maxime Danilo, Vijaykumar Chennupati, Joana Gomes Silva, Stefanie Siegert, Werner Held
The formation of central CD8 T cell memory in response to infection depends on the transcription factor Tcf1 (Tcf7). Tcf1 is expressed at high levels in naive CD8 T cells but downregulated in most CD8 T cells during effector differentiation. The relevance of Tcf1 downregulation for effector differentiation and the signals controlling Tcf1 expression have not been elucidated. Here, we show that systemic inflammatory signals downregulated Tcf1 in CD8 T cells during dendritic cell vaccination and bacterial infections...
February 20, 2018: Cell Reports
https://www.readbyqxmd.com/read/29466292/targeting-leukemia-stem-cells-in-the-bone-marrow-niche
#11
REVIEW
Sarah K Tasian, Martin Bornhäuser, Sergio Rutella
Abst ract: The bone marrow (BM) niche encompasses multiple cells of mesenchymal and hematopoietic origin and represents a unique microenvironment that is poised to maintain hematopoietic stem cells. In addition to its role as a primary lymphoid organ through the support of lymphoid development, the BM hosts various mature lymphoid cell types, including naïve T cells, memory T cells and plasma cells, as well as mature myeloid elements such as monocyte/macrophages and neutrophils, all of which are crucially important to control leukemia initiation and progression...
February 21, 2018: Biomedicines
https://www.readbyqxmd.com/read/29464806/histopathological-and-immunophenotypic-features-of-ipilimumab-associated-colitis-compared-to-ulcerative-colitis
#12
Brittany L Adler, Maryam K Pezhouh, Amy Kim, Lan Luan, Qingfeng Zhu, Faiz Gani, Mark Yarchoan, Jonathan Chen, Lysandra Voltaggio, Alyssa Parian, Mark Lazarev, Gregory Y Lauwers, Timothy M Pawlik, Elizabeth A Montgomery, Elizabeth Jaffee, Dung T Le, Janis M Taube, Robert A Anders
BACKGROUND: Use of the immune checkpoint inhibitor ipilimumab is sometimes complicated by ipilimumab-associated colitis (Ipi-AC), an immune-mediated colitis that mimics inflammatory bowel disease. OBJECTIVE: We sought to characterize the histopathologic and immunophenotypic features of Ipi-AC, and to directly compare these features to ulcerative colitis (UC). METHODS: This is a retrospective cohort study of 22 patients with Ipi-AC, 12 patients with treatment-naïve UC, and 5 controls with diarrhea but normal endoscopic findings...
February 21, 2018: Journal of Internal Medicine
https://www.readbyqxmd.com/read/29463691/sepsis-induced-t-cell-immunoparalysis-the-ins-and-outs-of-impaired-t-cell-immunity
#13
REVIEW
Isaac J Jensen, Frances V Sjaastad, Thomas S Griffith, Vladimir P Badovinac
Sepsis results in a deluge of pro- and anti-inflammatory cytokines, leading to lymphopenia and chronic immunoparalysis. Sepsis-induced long-lasting immunoparalysis is defined, in part, by impaired CD4 and CD8 αβ T cell responses in the postseptic environment. The dysfunction in T cell immunity affects naive, effector, and memory T cells and is not restricted to classical αβ T cells. Although sepsis-induced severe and transient lymphopenia is a contributory factor to diminished T cell immunity, T cell-intrinsic and -extrinsic factors/mechanisms also contribute to impaired T cell function...
March 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29463618/evaluation-of-the-role-of-stat3-in-antibody-and-t-h-17-mediated-responses-to-pneumococcal-immunization-and-infection-using-a-mouse-model-of-autosomal-dominant-hyper-ige-syndrome
#14
Kristin Moffitt, Elaine Cheung, John Manis, Richard Malley
Loss-of-function mutations in Signal Transducer and Activator of Transcription 3 gene ( stat3 ) result in Autosomal Dominant Hyper IgE Syndrome (AD-HIES), a condition in which patients have recurrent debilitating infections, including frequent pneumococcal and staphylococcal pneumonias. Stat3 mutations cause defective adaptive TH 17-cellular responses, an immune mechanism believed to be critical for clearance of pneumococcal colonization, and diminished antibody responses. Here we wished to evaluate the role of stat3 in clearance of pneumococcal carriage and immunity using mice with a stat3 mutation recapitulating AD-HIES...
February 20, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29462804/angiotensin-ii-regulates-th1-t-cell-differentiation-through-angiotensin-ii-type-1-receptor-pka-mediated-activation-of-proteasome
#15
Xian-Yun Qin, Yun-Long Zhang, Ya-Fei Chi, Bo Yan, Xiang-Jun Zeng, Hui-Hua Li, Ying Liu
BACKGROUND/AIMS: Naive CD4+ T cells differentiate into T helper cells (Th1 and Th2) that play an essential role in the cardiovascular diseases. However, the molecular mechanism by which angiotensin II (Ang II) promotes Th1 differentiation remains unclear. The aim of this study was to determine whether the Ang II-induced Th1 differentiation regulated by ubiquitin-proteasome system (UPS). METHODS: Jurkat cells were treated with Ang II (100 nM) in the presence or absence of different inhibitors...
February 15, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29461967/effects-of-lifelong-training-on-senescence-and-mobilization-of-t-lymphocytes-in-response-to-acute-exercise
#16
Luciele G Minuzzi, Luís Rama, Matheus Uba Chupel, Fátima Rosado, João Valente Dos Santos, Richard Simpson, António Martinho, Artur Paiva, Ana M Teixeira
BACKGROUND/PURPOSE: Ageing has profound impact on the immune system, mainly on T-cells. However, it has been suggested that chronic exercise may delay immunosenescence. Master athletes represent an interesting sub-demographic group to test this theory since they maintain a high training frequency and load throughout life. The purpose of this study was to evaluate the effects of lifelong training on the senescence and mobilization of T lymphocytes in response to acute exercise. MATERIAL AND METHODS: Nineteen athletes who regularly participated in training and competitions for more than 20 years throughout their lives and a control group of 10 healthy individuals participated in this study...
2018: Exercise Immunology Review
https://www.readbyqxmd.com/read/29460148/impact-of-vitamin-d-deficiency-on-clinical-parameters-in-treatment-na%C3%A3-ve-rheumatoid-arthritis-patients
#17
Yang Liu, Hongyan Wen
OBJECTIVE: To determine if patients with rheumatoid arthritis (RA) are at risk of vitamin D deficiency and whether the levels of vitamin D are correlated with clinical parameters in RA. METHODS: A total of 280 treatment-naïve RA patients, and 140 age- and sex-matched healthy volunteers were enrolled. Serum levels of 1,25-dihydroxycholecalciferol (1,25(OH)2 D3 ), the active form of vitamin D, were measured by enzyme-linked immunosorbent assay (ELISA). Concentrations of 1,25(OH)2 D3 less than 25 ng/mL were defined as insufficient...
February 19, 2018: Zeitschrift Für Rheumatologie
https://www.readbyqxmd.com/read/29460050/imaging-of-cytotoxic-antiviral-immunity-while-considering-the-3r-principle-of-animal-research
#18
Lucas Otto, Gennadiy Zelinskyy, Marc Schuster, Ulf Dittmer, Matthias Gunzer
Adoptive cell transfer approaches for antigen-specific CD8+ T cells are used widely to study their effector potential during infections or cancer. However, contemporary methodological adaptations regarding transferred cell numbers, advanced imaging, and the 3R principle of animal research have been largely omitted. Here, we introduce an improved cell transfer method that reduces the number of donor animals substantially and fulfills the requirements for intravital imaging under physiological conditions. For this, we analyzed the well-established Friend retrovirus (FV) mouse model...
February 19, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29459406/tlr2-stimulation-strengthens-intrahepatic-myeloid-derived-cell-mediated-t-cell-tolerance-through-inducing-kupffer-cell-expansion-and-il-10-production
#19
Jia Liu, Qing Yu, Weimin Wu, Xuan Huang, Ruth Broering, Melanie Werner, Michael Roggendorf, Dongliang Yang, Mengji Lu
Hepatic APCs play a critical role in promoting immune tolerance in the liver. Recently, we have demonstrated that TLR2 stimulation on liver sinusoidal endothelial cells reverted their suppressive properties to induce T cell immunity. However, there is a paucity of information about how TLR2 stimulation modulates the immunological function of other hepatic APCs. In the current study, we investigated whether TLR2 stimulation influences the function of intrahepatic myeloid-derived cells (iMDCs) and elucidated the mechanisms involved in iMDC-induced T cell immunity...
February 19, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29458681/broad-neutralization-response-in-a-subset-of-hiv-1-subtype-c-infected-viraemic-non-progressors-from-southern-india
#20
Paneerselvam Nandagopal, Jayanta Bhattacharya, Aylur K Srikrishnan, Rajat Goyal, Chinnambedu Ravichandran Swathirajan, Shilpa Patil, Shanmugam Saravanan, Suprit Deshpande, Ramachandran Vignesh, Sunil Suhas Solomon, Nikhil Singla, Joyeeta Mukherjee, Kailapuri G Murugavel
Broadly neutralizing antibodies (bnAbs) have been considered to be potent therapeutic tools and potential vaccine candidates to enable protection against various clades of human immunodeficiency virus (HIV). The generation of bnAbs has been associated with enhanced exposure to antigen, high viral load and low CD4+ T cell counts, among other factors. However, only limited data are available on the generation of bnAbs in viraemic non-progressors that demonstrate moderate to high viraemia. Further, since HIV-1 subtype C viruses account for more than 50 % of global HIV infections, the identification of bnAbs with novel specificities is crucial to enable the development of potent tools to aid in HIV therapy and prevention...
February 5, 2018: Journal of General Virology
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