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Helios T cell

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https://www.readbyqxmd.com/read/28881761/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...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28871165/zoonotic-intestinal-helminths-interact-with-the-canine-immune-system-by-modulating-t-cell-responses-and-preventing-dendritic-cell-maturation
#2
Johannes Junginger, Katharina Raue, Karola Wolf, Elisabeth Janecek, Veronika M Stein, Andrea Tipold, Anne-Rose Günzel-Apel, Christina Strube, Marion Hewicker-Trautwein
Parasite co-evolution alongside the mammalian immune system gave rise to several modulatory strategies by which they prevent exaggerated pathology and facilitate a longer worm survival. As little is known about the immunoregulatory potential of the zoonotic canine parasites Ancylostoma caninum and Toxocara canis in the natural host, the present study aimed to investigate whether their larval excretory-secretory (ES) products can modulate the canine immune system. We demonstrated TcES to increase the frequency of CD4+ Foxp3(high) T cells, while both AcES and TcES were associated with elevated Helios expression in Foxp3(high) lymphocytes...
September 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28757397/low-utility-of-serum-25-hydroxyvitamin-d3-and-1-25-dihydroxyvitamin-d3-in-predicting-peripheral-treg-and-th17-cell-counts-in-esrd-and-renal-transplant-patients
#3
Mostafa G Aly, Li Zhu, Rolf Weimer, Gerhard Opelz, Christian Morath, Ruben Kuon, Mohammed Tohamy, Gamal Saadi, Mona Soliman, Walaa Ibrahim, Volker Daniel
BACKGROUND: Vitamin D has shown an immune-modulatory effect in different studies. Vitamin D stimulates Tregs and inhibits Th17 cells. The immune-modulatory role of vitamin D in chronic kidney disease (CKD) and renal transplant patients is unclear. We measured whether different serum levels of vitamin D were associated with an increased or decreased presence of lymphocyte subsets including Treg and Th17 cells in end-stage renal disease (ESRD) and renal transplant recipients. METHODS: Eighty-seven renal transplant recipients and 53 end-stage renal disease (ESRD) patients were enrolled in this study...
July 27, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28747257/cells-with-treg-specific-foxp3-demethylation-but-low-cd25-are-prevalent-in-autoimmunity
#4
Ricardo C Ferreira, Henry Z Simons, Whitney S Thompson, Daniel B Rainbow, Xin Yang, Antony J Cutler, Joao Oliveira, Xaquin Castro Dopico, Deborah J Smyth, Natalia Savinykh, Meghavi Mashar, Tim J Vyse, David B Dunger, Helen Baxendale, Anita Chandra, Chris Wallace, John A Todd, Linda S Wicker, Marcin L Pekalski
Identification of alterations in the cellular composition of the human immune system is key to understanding the autoimmune process. Recently, a subset of FOXP3(+) cells with low CD25 expression was found to be increased in peripheral blood from systemic lupus erythematosus (SLE) patients, although its functional significance remains controversial. Here we find in comparisons with healthy donors that the frequency of FOXP3(+) cells within CD127(low)CD25(low) CD4(+) T cells (here defined as CD25(low)FOXP3(+) T cells) is increased in patients affected by autoimmune disease of varying severity, from combined immunodeficiency with active autoimmunity, SLE to type 1 diabetes...
July 23, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28690849/altered-regulatory-t-cell-fractions-and-helios-expression-in-clinically-isolated-syndrome-clues-to-the-development-of-multiple-sclerosis
#5
Anderson P Jones, Stephanie Trend, Scott N Byrne, Marzena J Fabis-Pedrini, Sian Geldenhuys, David Nolan, David R Booth, William M Carroll, Robyn M Lucas, Allan G Kermode, Prue H Hart
Development of multiple sclerosis (MS) is frequently preceded by an acute or subacute neurological disturbance referred to as clinically isolated syndrome (CIS). The specific immunological disturbances present in CIS remain underexamined. This study analysed peripheral blood mononuclear cells from n=18 treatment-naive individuals with recently diagnosed CIS (<120 days) for disturbances in the phenotype of T regulatory (Treg), follicular T regulatory (Tfr), T helper (Th), follicular T helper (Tfh) and B cells...
May 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28679297/evaluation-of-the-cytotoxic-response-mediated-by-perforin-and-granzyme-b-in-patients-with-non-hodgkin-lymphoma
#6
Bruna Maria Bereta Souza, Fernanda Bernadelli De Vito, Marianna Licati Calado, Marcos Vinícius Silva, Leonardo Rodrigues Oliveira, Virmondes Rodrigues-Júnior, Helio Moraes-Souza
This study quantified the perforin and granzyme B in patients with non-Hodgkin lymphoma (NHL) at the time of diagnosis. Protein quantification was performed by flow cytometry. NHL patients had a higher number of cytotoxic T lymphocytes (CTLs) expressing perforin as well as a greater number of activated CTLs than the control group. However, intracellular perforin levels in natural killer cells were lower in the NHL patients compared to the control group. Quantitative real time PCR showed that patients had more expression of perforin and granzyme B transcripts compared to the control group...
July 6, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28603527/intratumoral-foxp3-helios-regulatory-t-cells-upregulating-immunosuppressive-molecules-are-expanded-in-human-colorectal-cancer
#7
Azharuddin Sajid Syed Khaja, Salman M Toor, Haytham El Salhat, Bassam R Ali, Eyad Elkord
Regulatory T cells (Tregs) can be antitumorigenic or pro-tumorigenic in colorectal cancer (CRC) depending on the presence of different Treg subsets with various immunosuppressive molecules. Some studies reported the phenotypic characteristics of tumor-infiltrating immune cells in CRC, but limited studies have focused on the co-expression of suppressive molecules on immune cells. The aim of this study was to characterize immune cells in the tumor microenvironment (TME), compared to paired adjacent non-tumor colon tissue of CRC patients...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28566883/thiopurine-use-associated-with-reduced-b-and-natural-killer-cells-in-inflammatory-bowel-disease
#8
James D Lord, Donna M Shows
AIM: To identify which blood and mucosal lymphocyte populations are specifically depleted by thiopurine use in vivo. METHODS: The thiopurines azathioprine and 6-mercaptopurine have been a mainstay of inflammatory bowel disease (IBD) therapy for decades, but their mechanism of action in vivo remains obscure. Although thiopurines are lymphotoxic at high doses, and have been reported to cause T cell apoptosis in vitro, their ability to control IBD at lower doses suggests that they may selectively deplete particular lymphocyte populations...
May 14, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28467968/transcription-factor-c-rel-is-indispensable-for-generation-of-thymic-but-not-of-peripheral-foxp3-regulatory-t-cells
#9
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
#10
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
#11
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
#12
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
#13
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...
July 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28362433/il-2-prevents-deletion-of-developing-t-regulatory-cells-in-the-thymus
#14
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
#15
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
#16
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
#17
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
#18
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...
June 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
#19
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...
June 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
#20
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
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