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https://www.readbyqxmd.com/read/28721449/role-of-regulatory-t-cells-in-acute-myeloid-leukemia-patients-undergoing-relapse-preventive-immunotherapy
#1
Frida Ewald Sander, Malin Nilsson, Anna Rydström, Johan Aurelius, Rebecca E Riise, Charlotta Movitz, Elin Bernson, Roberta Kiffin, Anders Ståhlberg, Mats Brune, Robin Foà, Kristoffer Hellstrand, Fredrik B Thorén, Anna Martner
Regulatory T cells (Tregs) have been proposed to dampen functions of anti-neoplastic immune cells and thus promote cancer progression. In a phase IV trial (Re:Mission Trial, NCT01347996, http://www.clinicaltrials.gov ) 84 patients (age 18-79) with acute myeloid leukemia (AML) in first complete remission (CR) received ten consecutive 3-week cycles of immunotherapy with histamine dihydrochloride (HDC) and low-dose interleukin-2 (IL-2) to prevent relapse of leukemia in the post-consolidation phase. This study aimed at defining the features, function and dynamics of Foxp3(+)CD25(high)CD4(+) Tregs during immunotherapy and to determine the potential impact of Tregs on relapse risk and survival...
July 18, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28690613/relb-steady-state-migratory-dendritic-cells-control-the-peripheral-pool-of-the-natural-foxp3-regulatory-t-cells
#2
Anja Döhler, Theresa Schneider, Ina Eckert, Eliana Ribechini, Nico Andreas, Marc Riemann, Boris Reizis, Falk Weih, Manfred B Lutz
Thymus-derived natural Foxp3(+) CD4(+) regulatory T cells (nTregs) play a key role in maintaining immune tolerance and preventing autoimmune disease. Several studies indicate that dendritic cells (DCs) are critically involved in the maintenance and proliferation of nTregs. However, the mechanisms how DCs manage to keep the peripheral pool at constant levels remain poorly understood. Here, we describe that the NF-κB/Rel family transcription factor RelB controls the frequencies of steady-state migratory DCs (ssmDCs) in peripheral lymph nodes and their numbers control peripheral nTreg homeostasis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28599652/regulatory-t-cells-in-multiple-sclerosis-and-myasthenia-gravis
#3
REVIEW
K M Danikowski, S Jayaraman, B S Prabhakar
Multiple sclerosis (MS) is a chronic debilitating disease of the central nervous system primarily mediated by T lymphocytes with specificity to neuronal antigens in genetically susceptible individuals. On the other hand, myasthenia gravis (MG) primarily involves destruction of the neuromuscular junction by antibodies specific to the acetylcholine receptor. Both autoimmune diseases are thought to result from loss of self-tolerance, which allows for the development and function of autoreactive lymphocytes. Although the mechanisms underlying compromised self-tolerance in these and other autoimmune diseases have not been fully elucidated, one possibility is numerical, functional, and/or migratory deficits in T regulatory cells (Tregs)...
June 9, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28574228/apkc-%C3%AE-p-sp1-snail-signaling-induces-epithelial-mesenchymal-transition-and-immunosuppression-in-cholangiocarcinoma
#4
Yawei Qian, Wei Yao, Tao Yang, Yan Yang, Yan Liu, Qi Shen, Jian Zhang, Weipeng Qi, Jianming Wang
Cholangiocarcinoma (CCA) is a highly malignant bile duct cancer that tends to invade and metastasize early. The epithelial-mesenchymal transition (EMT) has been implicated in cancer cell invasion and metastasis, as well as in cancer cell evasion of host immunity. In this study, we investigated the interaction between atypical protein kinase C-iota (aPKC-ι) and Snail in the regulation of EMT and its relationship to CCA immunosuppression. Our results demonstrated that aPKC-ι, Snail, and infiltrated immunosuppressive cells were significantly up-regulated in CCA tumor tissues and were linked to poor prognosis...
June 2, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28351935/bidirectional-immune-tolerance-in-nonmyeloablative-mhc-mismatched-bmt-for-murine-%C3%AE-thalassemia
#5
Shuyu E, Aman Seth, Peter Vogel, Matt Sommers, Taren Ong, Asha B Pillai
Nonmyeloablative conditioning using total lymphoid irradiation (TLI) and rabbit antithymocyte serum (ATS) (the murine preclinical equivalent of antithymocyte globulin [ATG]) facilitates immune tolerance after bone marrow transplantation (BMT) across major histocompatibility complex (MHC) disparities and may be a useful strategy for nonmalignant disorders. We previously reported that donor effector T-cell function and graft-versus-host disease (GVHD) are regulated via recipient invariant natural killer T-cell (iNKT) interleukin-4-driven expansion of donor Foxp3(+) naturally occurring regulatory T cells (Tregs)...
June 1, 2017: Blood
https://www.readbyqxmd.com/read/28330901/azacitidine-mitigates-graft-versus-host-disease-via-differential-effects-on-the-proliferation-of-t-effectors-and-natural-regulatory-t-cells-in-vivo
#6
Matthew L Cooper, Jaebok Choi, Darja Karpova, Kiran Vij, Julie Ritchey, Mark A Schroeder, John F DiPersio
Azacitidine (AzaC) mitigates graft-versus-host disease (GvHD) in both murine preclinical transplant models and in human clinical trials while maintaining a robust graft-versus-leukemia effect. Previous studies have failed to investigate the role of natural regulatory T cells (nTregs) on the mitigation of GvHD by AzaC, instead focusing on the generation of suppressive Tregs (CD4(+)CD25(+)FOXP3(+)) through the in vivo conversion of alloreactive donor T effectors (Teffs; CD4(+)CD25(-)FOXP3(-)) and the direct antiproliferative effects of AzaC on allogeneic T cells...
May 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28286230/role-of-thymic-b-cells-in-the-development-of-thymus-derived-regulatory-t-cell-in-vitro
#7
Haider H Mohammed Ali, Nadzieja Drela
The thymus contains a low frequency of B cells, about 0.1-0.5% of total population of thymocytes that were shown to contribute in thymic negative selection. The fact that B cells in the periphery have been contributed in the generation of the T regulatory cell compartment emerged the idea that this process may indeed be initiated firstly within the thymus. The results of this study revealed that activated thymic B cells maintained the high percentage of nTreg generation or counteracted the decrease of this percentage observed in non-activated culture, and both activators (LPS and IMQ) have the same effect in the process of nTreg generation by B cells...
March 10, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28283017/forkhead-box-transcription-factor-1-affects-the-apoptosis-of-natural-regulatory-t-cells-by-controlling-aven-expression
#8
Zhitao Cai, Hong Liu, Xiongfei Wu
BACKGROUND: Regulatory T (Treg) cells play important roles in autoimmune diseases, cancer, and organ transplantation. Forkhead box protein o1 (Foxo1) and IL-7Rα(CD127) are closely related to the homeostasis of Treg cells. However, the mechanism underlying Treg proliferation and activation remains unclear. Here, we evaluated how the over-expression of Foxo1 affects Treg cell proliferation via intracellular signaling. nTreg cells were transfected separately with Foxo1 and Aven small-interfering RNA (siRNA) or over-expression plasmid...
March 10, 2017: BMC Immunology
https://www.readbyqxmd.com/read/28060341/in-vitro-differentiation-of-human-cd4-foxp3-induced-regulatory-t-cells-itregs-from-na%C3%A3-ve-cd4-t-cells-using-a-tgf-%C3%AE-containing-protocol
#9
Angelika Schmidt, Szabolcs Éliás, Rubin N Joshi, Jesper Tegnér
Regulatory T cells (Tregs) are an integral part of peripheral tolerance, suppressing immune reactions against self-structures and thus preventing autoimmune diseases. Clinical approaches to adoptively transfer Tregs, or to deplete Tregs in cancer, are underway with promising first outcomes. Because the number of naturally occurring Tregs (nTregs) is very limited, studying certain Treg features using in vitro induced Tregs (iTregs) can be advantageous. To date, the best although not absolutely specific protein marker to delineate Tregs is the transcription factor FOXP3...
December 30, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27999237/resting-and-activated-natural-tregs-decrease-in-the-peripheral-blood-of-patients-with-atherosclerosis
#10
Mohammadreza Yazdani, Shahdad Khosropanah, Ahmad Hosseini, Mehrnoosh Doroudchi
BACKGROUND: Atherosclerosis is a chronic inflammatory disease affecting large and medium arteries. CD4+ T cells are known to play a role in the progression of the disease. CD4+CD25+Foxp3+ natural Treg (nTreg) cells seem to have a protective role in the disease and their reduction in acute coronary syndrome is recently shown. OBJECTIVE: To investigate the frequency of nTreg subsets in the peripheral blood of patients with atherosclerosis. METHODS: Confirmation of atherosclerosis was done by angiography and 15 ml heparinized blood was obtained from each of the 13 non-diabetic patients and 13 non-diabetic, non-smoker individuals with normal/insignificant coronary artery disease confirmed by angiography...
December 2016: Iranian Journal of Immunology: IJI
https://www.readbyqxmd.com/read/27997080/prevention-of-allograft-rejection-by-use-of-regulatory-t-cells-with-an-mhc-specific-chimeric-antigen-receptor
#11
F Noyan, K Zimmermann, M Hardtke-Wolenski, A Knoefel, E Schulde, R Geffers, M Hust, J Huehn, M Galla, M Morgan, A Jokuszies, M P Manns, E Jaeckel
CD4(+) CD25(high) FOXP3(+) regulatory T cells (Tregs) are involved in graft-specific tolerance after solid organ transplantation. However, adoptive transfer of polyspecific Tregs alone is insufficient to prevent graft rejection even in rodent models, indicating that graft-specific Tregs are required. We developed a highly specific chimeric antigen receptor that recognizes the HLA molecule A*02 (referred to as A2-CAR). Transduction into natural regulatory T cells (nTregs) changes the specificity of the nTregs without alteration of their regulatory phenotype and epigenetic stability...
April 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/27988212/natural-regulatory-t-cells-from-patients-with-end-stage-renal-disease-can-be-used-for-large-scale%C3%A2-generation-of-highly-suppressive-alloantigen-specific-tregs
#12
Nicolle H R Litjens, Karin Boer, Joke M Zuijderwijk, Mariska Klepper, Annemiek M A Peeters, Wenda Verschoor, Rens Kraaijeveld, Michiel G H Betjes
Natural occurring regulatory T cells (nTregs) have the potential to offer a targeted approach of immunosuppression and are the cell type of interest for inducing tolerance in kidney transplantation. End-stage renal disease (ESRD) profoundly affects the composition and function of circulating T cells but little is known with respect to how nTreg potential is affected. To address this, nTregs of patients with ESRD (on dialysis or not) and healthy individuals were isolated, expanded using allogeneic mature monocyte-derived dendritic cells followed by anti-CD3/anti-CD28-coated beads and the different nTregs were extensively characterized by the demethylation status of the Treg-specific demethylated region within FOXP3 and expression of typical nTreg markers...
December 14, 2016: Kidney International
https://www.readbyqxmd.com/read/27936218/a-key-role-for-inhibins-in-dendritic-cell-maturation-and-function
#13
Roxana Olguín-Alor, Marisol de la Fuente-Granada, Laura C Bonifaz, Laura Antonio-Herrera, Eduardo A García-Zepeda, Gloria Soldevila
Inhibins are members of the TGFβ superfamily, which regulate many cellular processes including differentiation, proliferation, survival and apoptosis. Although initially described as hormones regulating the hypothalamus-pituitary-gonadal axis, based on their ability to antagonize Activins, our group has recently reported that they play a role in thymocyte differentiation and survival, as well as in thymic stromal cell maturation and nTreg generation. Here, we used Inhibin knock out mice (Inhα-/-) to investigate the role of Inhibins in peripheral dendritic cell maturation and function...
2016: PloS One
https://www.readbyqxmd.com/read/27824109/thymic-exosomes-promote-the-final-maturation-of-thymocytes
#14
Vanja Lundberg, Martin Berglund, Gabriel Skogberg, Susanne Lindgren, Christina Lundqvist, Judith Gudmundsdottir, Karolina Thörn, Esbjörn Telemo, Olov Ekwall
Extensive knowledge has been gained the last years concerning mechanisms underlying the selection of single positive thymocytes in the thymic medulla. Less is known regarding other important processes in the thymic medulla such as the regulation of late stage thymocyte maturation. We have previously reported that exosomes are abundant in the thymus with a phenotype that indicates an epithelial cell origin and immunoregulatory properties. In this study we use an in vitro system to investigate the effects of thymic exosomes on the maturation of single positive thymocytes as well as effects on nTreg formation...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27806875/immune-regulatory-effects-of-high-dose-vitamin-d3-supplementation-in-a-randomized-controlled-trial-in-relapsing-remitting-multiple-sclerosis-patients-receiving-ifn%C3%AE-the-solarium-study
#15
Anne-Hilde Muris, Joost Smolders, Linda Rolf, Marielle Thewissen, Raymond Hupperts, Jan Damoiseaux
Multiple sclerosis (MS) is characterized by a disturbed immune homeostasis and low serum vitamin D levels are associated with an increased disease activity. While vitamin D has been hypothesized to promote the maintenance of immune homeostasis, vitamin D supplementation could be of benefit to patients with MS. The SOLAR study investigated the effects of high dose vitamin D3 supplementation on clinical outcomes in a randomized controlled trial. Here we present the immune regulatory effects, investigated in the SOLARIUM sub-study...
November 15, 2016: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/27722210/regulatory-t-cell-therapy-for-graft-versus-host-disease
#16
Jessica Heinrichs, David Bastian, Anandharaman Veerapathran, Claudio Anasetti, Brain Betts, Xue-Zhong Yu
Graft-versus-host disease (GVHD) is a significant cause of non-relapse mortality after allogeneic hematopoietic cell transplantation (allo-HCT). Existing strategies to prevent and treat GVHD are incomplete, where a significant portion of allo-HCT recipients developed this complication. Despite this, one such therapy has emerged involving the use of regulatory T cells (Tregs) to control GVHD. The use of natural Tregs (nTregs) yielded positive pre-clinical results and are actively under investigation to reduce GVHD...
2016: Journal of Immunology Research and Therapy
https://www.readbyqxmd.com/read/27717665/type-2-innate-lymphoid-cell-suppression-by-regulatory-t%C3%A2-cells-attenuates-airway-hyperreactivity-and-requires-inducible-t-cell-costimulator-inducible-t-cell-costimulator-ligand-interaction
#17
Diamanda Rigas, Gavin Lewis, Jennifer L Aron, Bowen Wang, Homayon Banie, Ishwarya Sankaranarayanan, Lauriane Galle-Treger, Hadi Maazi, Richard Lo, Gordon J Freeman, Arlene H Sharpe, Pejman Soroosh, Omid Akbari
BACKGROUND: Atopic diseases, including asthma, exacerbate type 2 immune responses and involve a number of immune cell types, including regulatory T (Treg) cells and the emerging type 2 innate lymphoid cells (ILC2s). Although ILC2s are potent producers of type 2 cytokines, the regulation of ILC2 activation and function is not well understood. OBJECTIVE: In the present study, for the first time, we evaluate how Treg cells interact with pulmonary ILC2s and control their function...
May 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27581538/hepatic-stellate-cells-increase-the-immunosuppressive-function-of-natural-foxp3-regulatory-t-cells-via-ido-induced-ahr-activation
#18
Sudhir Kumar, Jiang Wang, Angus W Thomson, Chandrashekhar R Gandhi
Immunosuppressive, naturally occurring CD4(+)CD25(+)forkhead box p3(+) (Foxp3(+)) regulatory T cells (nTregs) offer potential for the treatment of immune-mediated inflammatory disorders. However, potential instability of ex vivo-expanded nTregs following their adoptive transfer may be a significant limitation. LPS-stimulated hepatic stellate cells (HSCs) induce expansion and enhance the suppressive function and stability of allogeneic nTregs We aimed to delineate mechanisms underlying HSC-induced expansion and increased potency of nTregs HSCs and nTregs were isolated from mouse livers and spleens, respectively...
August 31, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27571060/regulatory-cell-populations-in-relapsing-remitting-multiple-sclerosis-rrms-patients-effect-of-disease-activity-and-treatment-regimens
#19
Maria Rodi, Nikolaos Dimisianos, Anne-Lise de Lastic, Panagiota Sakellaraki, George Deraos, John Matsoukas, Panagiotis Papathanasopoulos, Athanasia Mouzaki
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) of autoimmune etiology that results from an imbalance between CNS-specific T effector cells and peripheral suppressive mechanisms mediated by regulatory cells (RC). In this research, we collected blood samples from 83 relapsing remitting MS (RRMS) patients and 45 healthy persons (HC), to assess the sizes of their RC populations, including CD4⁺CD25(high)Foxp3⁺ (nTregs), CD3⁺CD4⁺HLA(-)G⁺, CD3⁺CD8⁺CD28(-), CD3⁺CD56⁺, and CD56(bright) cells, and how RC are affected by disease activity (acute phase or remission) and types of treatment (methylprednisolone, interferon, or natalizumab)...
August 25, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27542981/inducible-and-naturally-occurring-regulatory-t%C3%A2-cells-enhance-lung-allergic-responses-through-divergent-transcriptional-pathways
#20
Anthony Joetham, Michaela Schedel, Brian P O'Connor, Soohyun Kim, Katsuyuki Takeda, Jordan Abbott, Erwin W Gelfand
BACKGROUND: Regulatory T cells attenuate development of asthma in wild-type (WT) mice, with both naturally occurring regulatory T (nTreg) cells and inducible regulatory T (iTreg) cells exhibiting suppressive activity. When transferred into CD8-deficient (CD8(-/-)) recipients, both cell types enhanced development of allergen-induced airway hyperresponsiveness. OBJECTIVE: We sought to determine whether the pathways leading to enhancement of lung allergic responses by transferred nTreg and iTreg cells differed...
April 2017: Journal of Allergy and Clinical Immunology
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