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Helios T cell

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https://www.readbyqxmd.com/read/28467968/transcription-factor-c-rel-is-indispensable-for-generation-of-thymic-but-not-of-peripheral-foxp3-regulatory-t-cells
#1
Maik Luu, Elena Jenike, Niyati Vachharajani, Alexander Visekruna
The transcription factor c-Rel has been shown to be crucial for development of regulatory T cells (Tregs). Recent studies have reported that the expression of transcription factor Helios in Foxp3+ Tregs correlates with thymic origin of these cells (tTregs). Notably, we found that only the Helios+Foxp3+ Treg cell population was substantially reduced in c-Rel deficient mice. In contrast to a defective tTreg development, we observed an expansion of mucosal Tregs during the induction of acute colitis in rel-/- mice...
April 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28401953/overexpression-of-heparanase-enhances-t-lymphocyte-activities-and-intensifies-the-inflammatory-response-in-a-model-of-murine-rheumatoid-arthritis
#2
Andreas Digre, Kailash Singh, Magnus Åbrink, Rogier M Reijmers, Stellan Sandler, Israel Vlodavsky, Jin-Ping Li
Heparanase is an endo-glucuronidase that degrades heparan sulfate chains. The enzyme is expressed at a low level in normal organs; however, elevated expression of heparanase has been detected in several inflammatory conditions, e.g. in the synovial joints of rheumatoid arthritis (RA) patients. Herein, we have applied the model of collagen-induced arthritis (CIA) to transgenic mice overexpressing human heparanase (Hpa-tg) along with wildtype (WT) mice. About 50% of the induced animals developed clinical symptoms, i...
April 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28401494/a-comparative-optical-coherence-tomography-study-of-spinocerebellar-ataxia-types-3-and-10
#3
Fernando Spina Tensini, Mario T Sato, Naoye Shiokawa, Tetsuo Ashizawa, Hélio A G Teive
SCA3 presents with a CAG expansion at 14q24.3-q32 while SCA10 shows an ATTCT expansion at 22q13-qter. SCA10 seems to be less aggressive than SCA3. For an in vivo, noninvasive approach of the correlation between central nervous system and clinical evolution, we can use optic coherence tomography (OCT) to measure retinal nerve fiber (RNFL) and ganglion cell layer (GCL) thickness. To describe OCT findings in SCA10, correlate it with expansion size and disease severity and compare with those of SCA3. We analyzed ten individuals with SCA3 and nine with SCA10 recruited from the neurology service of Hospital de Clínicas of Paraná-Brazil...
April 11, 2017: Cerebellum
https://www.readbyqxmd.com/read/28388539/preferential-accumulation-of-regulatory-t-cells-with-highly-immunosuppressive-characteristics-in-breast-tumor-microenvironment
#4
Azharuddin Sajid Syed Khaja, Salman M Toor, Haytham El Salhat, Issam Faour, Navid Ul Haq, Bassam R Ali, Eyad Elkord
Immunosuppressive cells such as regulatory T cells (Tregs) have an ambiguous role in breast cancer prognosis, with studies reporting both positive and negative correlations between Treg infiltration and prognosis. This discrepancy could be due to the different immunosuppressive molecules present in these cells. In the present study, we phenotypically characterize different Treg subsets infiltrating the tumor microenvironment (TME), compared to adjacent normal tissue and peripheral blood of primary breast cancer (PBC) patients...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28376432/expression-and-splicing-of-ikaros-family-members-in-murine-and-human-thymocytes
#5
Julie L Mitchell, Amara Seng, Thomas M Yankee
The Ikaros family of transcription factors includes five highly homologous members that can homodimerize or heterodimerize in any combination. Dimerization is essential for their ability to bind DNA and function as transcription factors. Previous studies showed that eliminating the function of the entire family blocks lymphocyte development while deletion of individual family members has relatively minor defects. These data indicate that multiple family members function during T cell development, so we examined the changes in expression of each family member as thymocytes progressed from the CD4(-)CD8(-) double negative (DN) to the CD4(+)CD8(+) double positive (DP) developmental stage...
April 1, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28362433/il-2-prevents-deletion-of-developing-t-regulatory-cells-in-the-thymus
#6
Daniel Y Hu, Rushika C Wirasinha, Christopher C Goodnow, Stephen R Daley
In the thymus, strongly self-reactive T cells may undergo apoptotic deletion or differentiate into Foxp3+ T-regulatory (T-reg) cells. Mechanisms that partition T cells into these two fates are unclear. Here, we show that IL-2 signalling is required to prevent deletion of CD4+ CD8- CCR7+ Helios+ thymocytes poised to upregulate Foxp3. The deletion prevented by IL-2 signalling is Foxp3 independent and occurs later in thymocyte development than the deletion that is prevented by Card11 signalling. Our results distinguish two bottlenecks at which strongly self-reactive thymocytes undergo deletion or progress to the next stage of T-reg differentiation; Card11 regulates the first bottleneck and IL-2 regulates the second...
June 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28345003/expansion-of-human-tregs-from-cryopreserved-umbilical-cord-blood-for-gmp-compliant-autologous-adoptive-cell-transfer-therapy
#7
Howard R Seay, Amy L Putnam, Judit Cserny, Amanda L Posgai, Emma H Rosenau, John R Wingard, Kate F Girard, Morey Kraus, Angela P Lares, Heather L Brown, Katherine S Brown, Kristi T Balavage, Leeana D Peters, Ashley N Bushdorf, Mark A Atkinson, Jeffrey A Bluestone, Michael J Haller, Todd M Brusko
Umbilical cord blood is a traditional and convenient source of cells for hematopoietic stem cell transplantation. Thymic regulatory T cells (Tregs) are also present in cord blood, and there is growing interest in the use of autologous Tregs to provide a low-risk, fully human leukocyte antigen (HLA)-matched cell product for treating autoimmune diseases, such as type 1 diabetes. Here, we describe a good manufacturing practice (GMP)-compatible Treg expansion protocol using fluorescence-activated cell sorting, resulting in a mean 2,092-fold expansion of Tregs over a 16-day culture for a median yield of 1...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28316600/methylation-of-foxp3-tsdr-underlies-the-impaired-suppressive-function-of-tregs-from-long-term-belatacept-treated-kidney-transplant-patients
#8
Evelyn Katy Alvarez Salazar, Arimelek Cortés-Hernández, Germán Rodrigo Alemán-Muench, Josefina Alberú, Jesús R Rodríguez-Aguilera, Félix Recillas-Targa, Victoria Chagoya de Sánchez, Eric Cuevas, Eduardo Mancilla-Urrea, María Pérez García, Guillermo Mondragón-Ramírez, Mario Vilatobá, Ian Bostock, Erick Hernández-Méndez, David De Rungs, Eduardo A García-Zepeda, Gloria Soldevila
Regulatory T cells (Tregs) are considered key players in the prevention of allograft rejection in transplanted patients. Belatacept (BLT) is an effective alternative to calcineurin inhibitors that appears to preserve graft survival and function; however, the impact of this drug in the homeostasis of Tregs in transplanted patients remains controversial. Here, we analyzed the phenotype, function, and the epigenetic status of the Treg-specific demethylated region (TSDR) in FOXP3 of circulating Tregs from long-term kidney transplant patients under BLT or Cyclosporine A treatment...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28301970/disclosing-the-parameters-leading-to-high-productivity-of-retroviral-producer-cells-lines-evaluating-random-versus-targeted-integration
#9
Vanessa S Bandeira, Hélio A Tomás, Evren Alici, Manuel J T Carrondo, Ana S Coroadinha
Gammaretrovirus and lentivirus are the preferred viral vectors to genetically modify T and natural killer cells to be used in immune cell therapies. The transduction efficiency of hematopoietic and T cells is more efficient using gibbon ape leukemia virus (GaLV) pseudotyping. In this context gammaretroviral vector producer cells offer competitive higher titers than transient lentiviral vectors productions. The main aim of this work was to identify the key parameters governing GaLV-pseudotyped gammaretroviral vector productivity in stable producer cells, using a retroviral vector expression cassette enabling positive (facilitating cell enrichment) and negative cell selection (allowing cell elimination)...
April 2017: Human Gene Therapy Methods
https://www.readbyqxmd.com/read/28286113/cd4-foxp3-t-regulatory-cell-subsets-in-myasthenia-gravis-patients
#10
Siegfried Kohler, Thomas Oskar Philipp Keil, Sarah Hoffmann, Marc Swierzy, Mahmoud Ismail, Jens Carsten Rückert, Tobias Alexander, Andreas Meisel
Although myasthenia gravis (MG) is a classic autoantibody-mediated disease, T cells are centrally involved in its pathogenesis. In recent years a number of studies have analyzed the role of CD4(+) FoxP3(+) regulatory T cells (Treg) in the disease with contradictory results. Here, the generation of Treg was significantly reduced in thymoma as compared to thymic hyperplasia and normal thymus tissue (p=0.0002). In the peripheral blood, Treg subsets classified according to CD49d, HELIOS and CD45RA expression changed after thymectomy and in the long-term course of immunosuppression...
March 9, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28284938/human-il-6r-hi-tigit-cd4-cd127-low-cd25-t-cells-display-potent-in-vitro-suppressive-capacity-and-a-distinct-th17-profile
#11
Ricardo C Ferreira, Daniel B Rainbow, Arcadio Rubio García, Marcin L Pekalski, Linsey Porter, João J Oliveira, Frank Waldron-Lynch, Linda S Wicker, John A Todd
To date many clinical studies aim to increase the number and/or fitness of CD4(+)CD127(low)CD25(+) regulatory T cells (Tregs) in vivo to harness their regulatory potential in the context of treating autoimmune disease. Here, we sought to define the phenotype and function of Tregs expressing the highest levels of IL-6 receptor (IL-6R). We have identified a population of CD4(+)CD127(low)CD25(+) TIGIT(-) T cells distinguished by their elevated IL-6R expression that lacked expression of HELIOS, showed higher CTLA-4 expression, and displayed increased suppressive capacity compared to IL-6R(hi)TIGIT(+) Tregs...
March 9, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28276457/cd40-signalling-abrogates-induction-of-ror%C3%AE-t-treg-cells-by-intestinal-cd103-dcs-and-causes-fatal-colitis
#12
Christian Barthels, Ana Ogrinc, Verena Steyer, Stefanie Meier, Ferdinand Simon, Maria Wimmer, Andreas Blutke, Tobias Straub, Ursula Zimber-Strobl, Esther Lutgens, Peggy Marconi, Caspar Ohnmacht, Debora Garzetti, Bärbel Stecher, Thomas Brocker
Immune homeostasis in intestinal tissues depends on the generation of regulatory T (Treg) cells. CD103(+) dendritic cells (DCs) acquire microbiota-derived material from the gut lumen for transport to draining lymph nodes and generation of receptor-related orphan γt(+) (RORγt(+)) Helios(-)-induced Treg (iTreg) cells. Here we show CD40-signalling as a microbe-independent signal that can induce migration of CD103(+) DCs from the lamina propria (LP) to the mesenteric lymph nodes. Transgenic mice with constitutive CD11c-specific CD40-signalling have reduced numbers of CD103(+) DCs in LP and a low frequency of RORγt(+)Helios(-) iTreg cells, exacerbated inflammatory Th1/Th17 responses, high titres of microbiota-specific immunoglobulins, dysbiosis and fatal colitis, but no pathology is detected in other tissues...
March 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28213366/tumor-infiltrating-and-peripheral-blood-t-cell-immunophenotypes-predict-early-relapse-in-localized-clear-cell-renal-cell-carcinoma
#13
Nicolas A Giraldo, Etienne Becht, Yann Vano, Florent Petitprez, Laetitia Lacroix, Pierre Validire, Rafael Sanchez-Salas, Alexandre Ingels, Stephane Marie Oudard, Audrey Moatti, Bénédicte Buttard, Sarah Bourras, Claire Germain, Xavier Cathelineau, Wolf-Herman Fridman, Catherine Sautes-Fridman
PURPOSE: The efficacy of PD-1 Checkpoint Blockade (ChB) as adjuvant therapy in localized clear cell Renal Cell Carcinoma (ccRCC) is currently unknown. The identification of tumor microenvironment (TME) prognostic biomarkers in this setting may help to define which patients could benefit from ChB and to uncover new therapeutic targets. EXPERIMENTAL DESIGN: We performed multiparametric flow cytometry immunophenotypic analysis of T cells isolated from tumor tissue (TIL), adjacent non-malignant renal tissue (RIL) and peripheral blood (PBL), in a cohort of patients (n=40) with localized ccRCC...
February 17, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28104514/increased-foxp3-helios-regulatory-t-cells-and-decreased-acute-graft-versus-host-disease-after-allogeneic-bone-marrow-transplantation-in-patients-receiving-sirolimus-and-rgi-2001-an-activator-of-invariant-natural-killer-t-cells
#14
Yi-Bin Chen, Yvonne A Efebera, Laura Johnston, Edward D Ball, David Avigan, Lazaros J Lekakis, Carlos R Bachier, Paul Martin, Omar Duramad, Yasuyuki Ishii, Semi Han, Yu-Jin Jung, Dana Lee, Lori Kunkel, Robert S Negrin, Jack D Bui
Regulatory T (Treg) cells play a central role in immune tolerance and prevention of aberrant immune responses. Several studies have suggested that the risk of graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT) can be ameliorated by increasing Tregs. We have developed an approach of in vivo expansion of Tregs with RGI-2001, a novel liposomal formulation of a synthetic derivative of alpha-galactosylceramide, a naturally occurring ligand that binds to CD1 and activates and expands invariant natural killer cells...
April 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28071216/disinhibition-of-the-rat-prelimbic-cortex-promotes-serotonergic-activation-of-the-dorsal-raphe-nucleus-and-panicolytic-like-behavioral-effects
#15
Paula Sm Yamashita, Ailton Spiacci, James E Hassel, Christopher A Lowry, Helio Zangrossi
Several studies have shown that serotonin plays a dual role in the modulation of defensive behaviors related to anxiety and panic. A major source of serotonergic projections to limbic structures responsible for this modulation is the dorsal raphe nucleus (DR). Anatomical studies indicate that the prelimbic (PL) cortex sends dense glutamatergic projections to the DR, leading to stimulation or inhibition of serotonin release in structures innervated by the DR. The objective of the present study was to investigate if GABAergic disinhibition of the PL by means of local administration of picrotoxin (PIC), a chloride channel blocker, can affect serotonergic tone and the expression of defensive behaviors related to anxiety and panic...
January 1, 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28006867/differential-profile-of-activated-regulatory-t-cell-subsets-and-micrornas-in-tolerant-liver-transplant-recipients
#16
B Revilla-Nuin, A de Bejar, L Martínez-Alarcón, J I Herrero, C M Martínez-Cáceres, P Ramírez, A Baroja-Mazo, J A Pons
Regulatory T cells (Tregs) play a potential role in operational tolerance in liver transplant patients, and microRNAs (miRNAs) are known to be involved in immunological responses and tolerance. Thus, we analyzed the implication of different peripheral blood Treg subsets and miRNAs on liver transplantation tolerance in 24 tolerant (Tol) and 23 non-tolerant (non-Tol) liver transplant recipients by cellular, genetic and epigenetic approximation. Non-Tol patients had a lower demethylation rate of the FOXP3 Treg-specific demethylated region (TSDR) than Tol patients that correlated with the frequency of circulating Tregs...
December 22, 2016: Liver Transplantation
https://www.readbyqxmd.com/read/27943367/analysis-of-mir-146a-and-mir-142-3p-as-potential-markers-of-freshly-isolated-or-in-vitro-expanded-human-treg-cells
#17
K Holmstrøm, A E Pedersen, M Gad
Regulatory CD4(+) T cells (Tregs) are pivotal for prevention of autoimmunity. The use of Tregs is therefore of increasing interest in in vitro drug screening assays as well as for a cytotherapy per se against autoimmune disorders. For both purposes, in vitro expansion of peripheral blood Tregs is necessary and there is an increasing need to identify novel markers that can discriminate natural thymic-derived Tregs (tTregs) from other T cell subsets, and ideally, such markers should be stably expressed during in vitro expansion procedures...
February 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/27880974/deep-sequencing-of-the-tcr-%C3%AE-repertoire-of-human-forkhead-box-protein-3-foxp3-and-foxp3-t-cells-suggests-that-they-are-completely-distinct-and-non-overlapping
#18
A Golding, S Darko, W H Wylie, D C Douek, E M Shevach
Maintenance of peripheral tolerance requires a balance between autoreactive conventional T cells (Tconv ) and thymically derived forkhead box protein 3 (FoxP3)(+) regulatory T cells (tTregs ). Considerable controversy exists regarding the similarities/differences in T cell receptor (TCR) repertoires expressed by Tconv and tTregs . We generated highly purified populations of human adult and cord blood Tconv and tTregs based on the differential expression of CD25 and CD127. The purity of the sorted populations was validated by intracellular staining for FoxP3 and Helios...
April 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27834805/tapirira-guianensis-aubl-extracts-inhibit-proliferation-and-migration-of-oral-cancer-cells-lines
#19
Renato José Silva-Oliveira, Gabriela Francine Lopes, Luiz Fernando Camargos, Ana Maciel Ribeiro, Fábio Vieira Dos Santos, Richele Priscila Severino, Vanessa Gisele Pasqualotto Severino, Ana Paula Terezan, Ralph Gruppi Thomé, Hélio Batista Dos Santos, Rui Manuel Reis, Rosy Iara Maciel de Azambuja Ribeiro
Cancer of the head and neck is a group of upper aerodigestive tract neoplasms in which aggressive treatments may cause harmful side effects to the patient. In the last decade, investigations on natural compounds have been particularly successful in the field of anticancer drug research. Our aim is to evaluate the antitumor effect of Tapirira guianensis Aubl. extracts on a panel of head and neck squamous cell carcinoma (HNSCC) cell lines. Analysis of secondary metabolites classes in fractions of T. guianensis was performed using Nuclear Magnetic Resonance (NMR)...
November 8, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27826566/variations-in-mrna-and-protein-levels-of-ikaros-family-members-in-pediatric-t-cell-acute-lymphoblastic-leukemia
#20
Julie L Mitchell, Thomas M Yankee
BACKGROUND: Pediatric T cell acute lymphoblastic leukemia (T-ALL) is a highly heterogeneous disease in which the cells share phenotypic characteristics with normal human thymocytes. The Ikaros family of transcription factors includes five members that are required for normal T cell development and are implicated in leukemogenesis. The goal of this work was to correlate the pattern of expression of Ikaros family members with the phenotype of the T-ALL cells. METHODS: We obtained twenty-four samples from pediatric T-ALL patients and used multi-parameter flow cytometry to characterize each sample, comparing the phenotype of the leukemic cells with normal human thymocytes...
October 2016: Annals of Translational Medicine
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