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https://www.readbyqxmd.com/read/29792274/ex-vivo-expanded-natural-regulatory-t-cells-from-patients-with-end-stage-renal-disease-or-kidney-transplantation-are-useful-for-autologous-cell-therapy
#1
Sybille Landwehr-Kenzel, Anne Zobel, Henrike Hoffmann, Niels Landwehr, Michael Schmueck-Henneresse, Thomas Schachtner, Andy Roemhild, Petra Reinke
Novel concepts employing autologous, ex vivo expanded natural regulatory T cells (nTreg) for adoptive transfer has potential to prevent organ rejection after kidney transplantation. However, the impact of dialysis and maintenance immunosuppression on the nTreg phenotype and peripheral survival is not well understood, but essential when assessing patient eligibility. The current study investigates regulatory T-cells in dialysis and kidney transplanted patients and the feasibility of generating a clinically useful nTreg product from these patients...
June 2018: Kidney International
https://www.readbyqxmd.com/read/29757588/association-of-regulatory-t-cells-with-diabetes-type-1-and-its-renal-and-vascular-complications-based-on-the-expression-of-forkhead-box-protein-p3-foxp3-helios-and-neurophilin-1
#2
Tahereh Khamechian, Behnaz Irandoust, Hanieh Mohammadi, Hassan Nikoueinejad, Hossein Akbari
In recent years, it has been recognized that regulatory T cells (Tregs) play a critical role in maintaining immune tolerance. Moreover, the expression of two markers named Helios and neurophilin-1 (NRP-1) has been highlighted in such cells. Helios, an intracellular transcription marker, largely differentiates twomost operative sub group of Tregs, namely naturally occurring (nTreg) and induced (iTreg) Tregs, and NRP-1 is reckoned as a membranous activity marker of Tregs. We aimed to count peripheral mononuclear cells expressing such markers in a group of type 1 diabetes patients to elucidate the possible role of Tregs in the pathogenesis of such disease and its complications...
April 2018: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/29728642/a-model-of-th17-associated-ileal-hyperplasia-that-requires-both-il-17a-and-ifn%C3%AE-to-generate-self-tolerance-and-prevent-colitis
#3
Jonathan C Jeschke, Christopher G Mayne, Jennifer Ziegelbauer, Christopher L DeCiantis, Selina Singh, Suresh N Kumar, Mariko Suchi, Yoichiro Iwakura, William R Drobyski, Nita H Salzman, Calvin B Williams
Homeostasis in the ileum, which is commonly disrupted in patients with Crohn's disease, involves ongoing immune responses. To study how homeostatic processes of the ileum impact CD4+ T cell responses, we used TCR transgenic tools to breed mice that spontaneously produced CD4+ T cells reactive to an antigen expressed in the ileum. At an early age, the ilea of these mice exhibit crypt hyperplasia and accumulate increased numbers of TH 17 cells bearing non-transgenic clonotypes. Half of these mice subsequently developed colitis linked to broad mucosal infiltration by TH 17 and TH 1 cells expressing non-transgenic clonotypes, chronic wasting disease and loss of ileal crypt hyperplasia...
May 4, 2018: Mucosal Immunology
https://www.readbyqxmd.com/read/29686686/autoimmune-lymphoproliferative-syndrome-fas-patients-have-an-abnormal-regulatory-t-cell-treg-phenotype-but-display-normal-natural-treg-suppressive-function-on-t-cell-proliferation
#4
Fabienne Mazerolles, Marie-Claude Stolzenberg, Olivier Pelle, Capucine Picard, Benedicte Neven, Alain Fischer, Aude Magerus-Chatinet, Frederic Rieux-Laucat
Objective: Autoimmune lymphoproliferative syndrome (ALPS) with FAS mutation (ALPS-FAS) is a nonmalignant, noninfectious, lymphoproliferative disease with autoimmunity. Given the central role of natural regulatory T cells (nTregs) in the control of lymphoproliferation and autoimmunity, we assessed nTreg-suppressive function in 16 patients with ALPS-FAS. Results: The proportion of CD25high CD127low Tregs was lower in ALPS-FAS patients than in healthy controls. This subset was correlated with a reduced CD25 expression in CD3+ CD4+ T cells from ALPS patients and thus an abnormally low proportion of CD25high FOXP3+ Helios+ T cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29306022/t-regulatory-cells-mediate-immunosuppresion-by-adenosine-in-peripheral-blood-sentinel-lymph-node-and-tils-from-melanoma-patients
#5
P Di Gennaro, G Gerlini, R Caporale, S Sestini, P Brandani, C Urso, N Pimpinelli, L Borgognoni
T regulatory cells (Tregs), involved in tumour tolerance, can generate Adenosine by CD39/CD73 surface enzymes, which identify four Tregs subsets: CD39+ CD73- nTregs, CD39+ CD73+ iTregs, CD39- CD73+ oTregs and CD39- CD73- xTregs. In melanoma patients, increased Tregs levels are detected in peripheral blood (PB), sentinel lymph node (SLN) and tumour infiltrating lymphocytes (TILs), but Adenosine role was not investigated yet. We examined total Tregs and Adenosine subsets in PB, SLN and TILs from melanoma patients (n = 32) and PB from healthy donors (HD; n = 10) by flow cytometry...
March 28, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29285209/combination-of-il-2-rapamycin-dna-methyltransferase-and-histone-deacetylase-inhibitors-for-the-expansion-of-human-regulatory-t-cells
#6
Makoto Miyara, Driss Chader, Aude Burlion, Jérémie Goldstein, Delphine Sterlin, Françoise Norol, Hélène Trebeden-Nègre, Laetitia Claër, Shimon Sakaguchi, Gilles Marodon, Zahir Amoura, Guy Gorochov
FOXP3+ regulatory T cell (Treg) based cellular therapies represent promising therapeutic options in autoimmunity, allergy, transplantation and prevention of Graft Versus Host (GVH) Disease. Among human FOXP3-expressing CD4+ T cells, only the CD45RA+ naïve Treg (nTreg) subset is suitable for in vitro expansion. However, FoxP3 expression decays in cells using currently described culture protocols. Rapamycin alone was not able to prevent FOXP3 loss in nTregs cells, as only a half of them maintained FOXP3 expression after 14 days of culture...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29057512/induction-of-porcine-specific-regulatory-t-cells-with-high-specificity-and-expression-of-il-10-and-tgf-%C3%AE-1-using-baboon-derived-tolerogenic-dendritic-cells
#7
Mingqian Li, Judith Eckl, Jan-Michael Abicht, Tanja Mayr, Bruno Reichart, Dolores J Schendel, Heike Pohla
BACKGROUND: Regulatory T cells (Treg) play an important role in maintenance of homeostasis in vivo. Treg application to alleviate allo-organ rejection is being studied extensively. However, natural Treg (nTreg) expansion in vitro is laborious and expensive. Antigen-specific Treg are more effective and require lower cell numbers than use of nTreg for immune control. The baboon, as a non-human primate experimental animal model, is widely used in xenotransplantation research. An effective method to generate baboon xeno-specific Treg would benefit research on immune tolerance in xenotransplantation using this model system...
January 2018: Xenotransplantation
https://www.readbyqxmd.com/read/28891726/nk-cell-effector-functions-regulation-by-modulating-ntreg-cell-population-during-progressive-growth-of-dalton-s-lymphoma-in-mice
#8
Munendra Singh Tomar, Sanjay Kumar, Sanjay Kumar, Pramod Kumar Gautam, Rishi Kant Singh, Praveen Kumar Verma, Surya Pratap Singh, Arbind Acharya
Natural killer (NK) cells are large granular lymphocytes of the innate immune system and play a pivotal role against virus-infected cells, microbial pathogens, and tumor cells. NK cells secrete several cytokine,s but IFN-γ secreted by NK cells play a vital role in the activation of the innate and adaptive immune systems. But during any infection or tumor burden, functional activity of NK cells is downregulated significantly by nTreg cells. It is also found that during tumor progression, the number of nTreg cells increases as a result; it effectively suppresses the antitumor activity of NK cells...
January 2018: Immunological Investigations
https://www.readbyqxmd.com/read/28804811/serum-diamine-oxidase-in-pseudoallergy-in-the-pediatric-population
#9
Joanna Kacik, Barbara Wróblewska, Sławomir Lewicki, Robert Zdanowski, Bolesław Kalicki
Histamine intolerance (pseudoallergy) is a poorly investigated type of food hypersensitivity. The main enzyme responsible for histamine degradation in the extracellular matrix is diamine oxidase (DAO). Disturbances in the concentration or activity of DAO may lead to the development of clinical signs of allergy. The aim of the present work was to assess the DAO concentration, peripheral blood morphology, lymphocytes phenotyping (CD3+, CD4+, CD8+, CD19+, NK cells, NKT cells, and activated T-cells), and natural regulatory Treg (nTregs) cell population (CD4+, CD25+, CD127low, and FoxP3) in 34 pediatric patients with histamine-dependent syndromes...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28736999/regulatory-t-cell-subsets-in-peripheral-blood-of-celiac-disease-patients-and-tlr2-expression-correlation-with-oxidative-stress
#10
Sanjay Kumar, Sadhna Lal, Archana Bhatnagar
The study was carried out to study expression of Toll like receptors 2 (TLR2), natural/inducible Treg and Interferon-γ alongside oxidative stress and understand their significance in pediatric samples. Influence of oxidative stress on Celiac Disease was analysed by evaluating lipid peroxidation, reduced glutathione, Glutathione peroxidase, etc. A comparison was performed among CD patients, CD patients on gluten free diet (GFD), and healthy controls. Peripheral nTregs exhibited a similar pattern of reduced numbers in CD and GFD cases when compared to healthy controls...
October 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28729608/programmed-death-one-homolog-maintains-the-pool-size-of-regulatory-t-cells-by-promoting-their-differentiation-and-stability
#11
Qi Wang, Jianwei He, Dallas B Flies, Liqun Luo, Lieping Chen
Programmed death one homolog (PD-1H) is an immunoglobulin superfamily molecule and primarily acts as a coinhibitor in the initiation of T cell response to antigens. Here, we report that genetic ablation of PD-1H in mice blocks the differentiation of naive T cells to Foxp3(+) inducible Treg cells (iTreg) with a significant decrease of iTreg in lymphoid organs. This effect of PD-1H is highly specific for iTreg because both naturally generated iTreg in gut-related tissues and in vitro induced iTreg by TGF-β were decreased whereas the genesis of natural Treg (nTreg) remains normal...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28721449/role-of-regulatory-t-cells-in-acute-myeloid-leukemia-patients-undergoing-relapse-preventive-immunotherapy
#12
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+ CD25high CD4+ Tregs during immunotherapy and to determine the potential impact of Tregs on relapse risk and survival...
November 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
#13
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
#14
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
#15
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 linked to poor prognosis...
October 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
#16
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
#17
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
#18
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...
May 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
#19
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
#20
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
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