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Foxp3 transplant

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https://www.readbyqxmd.com/read/29783997/graft-protective-effect-and-induction-of-cd4-foxp3-cell-by-thrombomodulin-on-allograft-arteriosclerosis-in-mice
#1
Enzhi Yin, Shigefumi Matsuyama, Masateru Uchiyama, Kento Kawai, Masanori Niimi
BACKGROUND: Thrombomodulin (TM) is a promising therapeutic natural anti-coagulant, which exerts the effects to control disseminated intravascular coagulation. However, little is known whether TM on micro-vessels could play an important role in the regulation of intimal hyperplasia. We investigated the vessel-protective effect of TM in the survival of fully major histocompatibility complex (MHC)-mismatched murine cardiac allograft transplantation. METHODS: CBA recipients transplanted with a C57BL/6 heart received intraperitoneal administration of normal saline or 0...
May 21, 2018: Journal of Cardiothoracic Surgery
https://www.readbyqxmd.com/read/29769260/bim-regulates-the-survival-and-suppressive-capability-of-cd8-foxp3-regulatory-t-cells-during-murine-gvhd
#2
Kimberle Agle, Benjamin G Vincent, Clint Piper, Ludovic Belle, Vivian Zhou, Warren Shlomchik, Jonathan S Serody, William R Drobyski
CD8+ Foxp3+ T cells (Tregs) are a potent regulatory population whose functional and ontological similarities to CD4+ Fox3+ T cells have not been well delineated. Using an experimental model of graft versus host disease (GVHD), we observed that CD8+ Tregs were significantly less potent than CD4+ Tregs for the suppression of GVHD. To define the mechanistic basis for this observation, we examined the T cell repertoire and the transcriptional profile of in vivo-derived CD4+ and CD8+ Tregs that emerged early during this disease...
May 16, 2018: Blood
https://www.readbyqxmd.com/read/29752140/feiji-recipe-inhibits-the-growth-of-lung-cancer-by-modulating-t-cell-immunity-through-indoleamine-2-3-dioxygenase-pathway-in-an-orthotopic-implantation-model
#3
Bin Luo, Zu-Jun Que, Zhi-Yi Zhou, Qing Wang, Chang-Sheng Dong, Yi Jiang, Bing Hu, Hui Shi, Yu Jin, Jian-Wen Liu, He-Gen Li, Lin Wang, Jian-Hui Tian
OBJECTIVE: Escape from the body's immune response is a basic characteristic of lung cancer, and indoleamine-2,3-dioxygenase (IDO) plays a key role in mediating immune escape of non-small-cell lung cancer, which leads to recurrence and metastasis. Feiji Recipe, a compound Chinese herbal medicine, has the effect of stabilizing lesions and prolonging survival in patients with lung cancer. The purpose of this study was to investigate the mechanisms underlying the anticancer properties of Feiji Recipe...
April 22, 2018: Journal of Integrative Medicine
https://www.readbyqxmd.com/read/29751114/very-low-numbers-of-cd4-foxp3-tregs-expanded-in-donors-via-tl1a-ig-and-low-dose-il-2-exhibit-a-distinct-activation-functional-profile-and-suppress-gvhd-in-a-pre-clinical-model
#4
Sabrina Copsel, Dietlinde Wolf, Brandon Kale, Henry Barreras, Casey O Lightbourn, Cameron S Bader, W Alperstein, Norman H Altman, Krishna V Komanduri, Robert B Levy
Regulatory T cells (Tregs) are essential for the maintenance of tolerance and immune homeostasis. In allogeneic hematopoietic stem cell transplantation (aHSCT), transfer of appropriate Treg numbers is a promising therapy for the prevention of graft-versus-host disease (GVHD). We have recently reported a novel approach which induces the marked expansion and selective activation of Tregs in vivo by targeting TNF receptor superfamily 25 (TNFRSF25) and CD25. A potential advance to promote clinical application of Treg cells to ameliorate GVHD and other disorders would be the generation of more potent Treg populations...
May 8, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29743501/a-phase-i-clinical-trial-with-ex-vivo-expanded-recipient-regulatory-t-cells-in-living-donor-kidney-transplants
#5
James M Mathew, Jessica H-Voss, Ann LeFever, Iwona Konieczna, Cheryl Stratton, Jie He, Xuemei Huang, Lorenzo Gallon, Anton Skaro, Mohammed Javeed Ansari, Joseph R Leventhal
There is considerable interest in therapeutic transfer of regulatory T cells (Tregs) for controlling aberrant immune responses. Initial clinical trials have shown the safety of Tregs in hematopoietic stem cell transplant recipients and subjects with juvenile diabetes. Our hypothesis is that infusion(s) of Tregs may induce transplant tolerance thus avoiding long-term use of toxic immunosuppressive agents that cause increased morbidity/mortality. Towards testing our hypothesis, we conducted a phase I dose escalation safety trial infusing billions of ex vivo expanded recipient polyclonal Tregs into living donor kidney transplant recipients...
May 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29731774/b7-h1-expression-is-required-for-human-endometrial-regenerative-cells-in-the-prevention-of-transplant-vasculopathy-in-mice
#6
Kui Ye, Xu Lan, Grace Wang, Baoren Zhang, Xiaoxi Xu, Xiang Li, Yiming Zhao, Hao Wang
Vasculopathy is one of the primary pathological changes in chronic rejection of vascularized allograft transplantation. Endometrial regenerative cells (ERCs) are mesenchymal-like stromal cells with immunosuppressive effect. B7-H1 is a negative costimulator that mediates active immune suppression. The aim of this study was to investigate the requirement of B7-H1 in the immunoregulation of ERCs in preventing transplant vasculopathy of aorta allografts. The results showed that B7-H1 expression on ERCs was upregulated by IFN- γ in a dose-dependent manner and it was required for ERCs to inhibit the proliferation of peripheral blood mononuclear cells (PBMCs) in vitro ...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29728574/pathological-conversion-of-regulatory-t-cells-is-associated-with-loss-of-allotolerance
#7
Jing Hua, Takenori Inomata, Yihe Chen, William Foulsham, William Stevenson, Tina Shiang, Jeffrey A Bluestone, Reza Dana
CD4+ CD25+ Foxp3+ Regulatory T cells (Tregs) play a critical role in immune tolerance. The plasticity and functional adaptability of Tregs in an inflammatory microenvironment has been demonstrated in autoimmunity. Here, using a double transgenic mouse model that permits Foxp3 lineage tracing, we investigated the phenotypic plasticity of Foxp3+ Tregs in a well-characterized murine model of corneal transplantation. In order to subvert the normal immune privilege of the cornea and foster an inflammatory milieu, host mice were exposed to desiccating stress prior to transplantation...
May 4, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29728401/immune-regulatory-cell-infusion-for-graft-versus-host-disease-prevention-and-therapy
#8
Bruce R Blazar, Kelli P A MacDonald, Geoffrey R Hill
Current approaches to prevent and treat graft-versus-host disease (GVHD) after stem cell transplantation rely principally on pharmacological immune suppression. Such approaches are limited by drug toxicity, non-specific immune suppression and a requirement for long-term therapy. Our increased understanding of the regulatory cells and molecular pathways involved in limiting pathogenic immune responses opens the opportunity for the use of these cell subsets to prevent and/or GVHD. The theoretical advantages of this approach is permanency of effect, potential for facilitating tissue repair, and induction of tolerance that obviates a need for ongoing drug therapy...
May 4, 2018: Blood
https://www.readbyqxmd.com/read/29698799/blimp-1-prolongs-allograft-survival-without-regimen-via-influencing-t-cell-development-in-favor-of-regulatory-t-cells-while-suppressing-th1
#9
Aline Yen Ling Wang, Charles Yuen Yung Loh, Shyi-Jou Chen, Huang-Kai Kao, Cheng-Hung Lin, Sheng-Hao Chuang, Chin-Ming Lee, Huey-Kang Sytwu, Fu-Chan Wei
BACKGROUND: B lymphocyte-induced maturation protein 1 (Blimp-1) transcription factor is expressed in multiple cell lineages and in particular, T cells. However, the role of Blimp-1 in T cell-mediated allograft tolerance is still unknown. METHODS: This study is the first to investigate transplanted skin allograft survival using transgenic (Tg) mice with T cell overexpression of Blimp-1. RESULTS: Without any immunosuppression, fully MHC-mismatched skin allografts on Tg(+) mice had a significantly prolonged survival rate and partial tolerance at 90 days...
April 23, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29686677/mir-466a-targeting-of-tgf-%C3%AE-2-contributes-to-foxp3-regulatory-t-cell-differentiation-in-a-murine-model-of-allogeneic-transplantation
#10
William Becker, Mitzi Nagarkatti, Prakash S Nagarkatti
The promise of inducing immunological tolerance through regulatory T cell (Treg) control of effector T cell function is crucial for developing future therapeutic strategies to treat allograft rejection as well as inflammatory autoimmune diseases. In the current study, we used murine allograft rejection as a model to identify microRNA (miRNA) regulation of Treg differentiation from naïve CD4 cells. We performed miRNA expression array in CD4+ T cells in the draining lymph node (dLN) of mice which received syngeneic or allogeneic grafts to determine the molecular mechanisms that hinder the expansion of Tregs...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29673063/uv-light-crosslinking-regresses-mature-corneal-blood-and-lymphatic-vessels-and-promotes-subsequent-high-risk-corneal-transplant-survival
#11
Yanhong Hou, Viet Nhat Hung Le, Gábor Tóth, Sebastian Siebelmann, Jens Horstmann, Tim Gabriel, Felix Bock, Claus Cursiefen
Immunological graft rejection is the main complication after corneal transplantation into pathologically prevascularized so-called high risk eyes. Aim of this study was to evaluate whether UV-light crosslinking can regress pathological corneal blood and lymphatic vessels, and thereby improve subsequent graft survival. Using the murine model of suture-induced corneal neovascularization, we found that corneal crosslinking with ultraviolet (UV) A-light and riboflavin regressed both preexisting blood and lymphatic vessels significantly via inducing apoptosis in vascular endothelial cells...
April 19, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29670207/homeostatic-proliferation-leads-to-telomere-attrition-and-increased-pd-1-expression-after-autologous-hematopoietic-sct-for-systemic-sclerosis
#12
Lucas C M Arruda, João R Lima-Júnior, Emmanuel Clave, Daniela A Moraes, Corinne Douay, Isabelle Fournier, Hélène Moins-Teisserenc, Dimas T Covas, Belinda P Simões, Dominique Farge, Antoine Toubert, Kelen C R Malmegrim, Maria Carolina Oliveira
In the months that follow autologous hematopoietic stem cell transplantation (AHSCT), lymphopenia drives homeostatic proliferation, leading to oligoclonal expansion of residual cells. Here we evaluated how replicative senescent and exhausted cells associated with clinical outcomes of 25 systemic sclerosis (SSc) patients who underwent AHSCT. Patients were clinically monitored for skin (modified Rodnan's skin score, mRSS) and internal organ involvement and had blood samples collected before and semiannually, until 3 years post-AHSCT, for quantification of telomere length, CD8+ CD28- and PD-1+ cells, and serum cytokines...
April 18, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29622483/mesenchymal-stromal-cell-exosome-enhanced-regulatory-t-cell-production-through-an-antigen-presenting-cell-mediated-pathway
#13
Bin Zhang, Ronne Wee Yeh Yeo, Ruenn Chai Lai, Eugene Wei Kian Sim, Keh Chuang Chin, Sai Kiang Lim
BACKGROUND AIMS: The immunomodulatory property of mesenchymal stromal cell (MSC) exosomes is well documented. On the basis of our previous report that MSC exosomes increased regulatory T-cell (Treg) production in mice with allogenic skin graft but not in ungrafted mice, we hypothesize that an activated immune system is key to exosome-mediated Treg production. METHODS: To test our hypothesis, MSC exosomes were incubated with mouse spleen CD4+ T cells that were activated with either anti-CD3/CD28 mAbs or allogenic antigen-presenting cell (APC)-enriched spleen CD11c+ cells to determine whether production of mouse CD4+ CD25+ T cells or CD4+ CD25+ Foxp3+ Tregs could be induced...
April 2, 2018: Cytotherapy
https://www.readbyqxmd.com/read/29614336/peripheral-blood-immune-response-related-gene-analysis-for-evaluating-the-potential-risk-of-chronic-antibody-mediated-rejection
#14
Takayuki Yamamoto, Kenta Iwasaki, Kenta Murotani, Asami Takeda, Kenta Futamura, Manabu Okada, Makoto Tsujita, Takahisa Hiramitsu, Norihiko Goto, Shunji Narumi, Yoshihiko Watarai, Kunio Morozumi, Kazuharu Uchida, Takaaki Kobayashi
Noninvasive methods for the early diagnosis of chronic antibody-mediated rejection (cAMR) are desired for patients with de novo (dn) donor-specific HLA antibody (DSA). This study aimed to elucidate the clinical relevance of immune-related gene expression in peripheral blood of kidney transplant recipients. The expression levels of fourteen key molecules (Foxp3, CTLA-4, CCR7, TGF-β, IGLL-1, IL-10, ITCH, CBLB, Bcl-6, CXCR5, granzyme B, CIITA, Baff, TOAG-1/TCAIM) related to regulatory/cytotoxic function of immune cells were compared in 93 patients, which were divided into Groups A (clinical cAMR with dn DSA, n=16), B (subclinical cAMR with dn DSA, n=17), C (negative cAMR with dn DSA, n=21) and D (stable function without dn DSA, n=39)...
March 31, 2018: Human Immunology
https://www.readbyqxmd.com/read/29603600/histone-protein-deacetylase-inhibitor-therapy-for-enhancement-of-foxp3-t-regulatory-cell-function-post-transplantation
#15
L Wang, U H Beier, T Akimova, S Dahiya, R Han, A Samanta, M H Levine, W W Hancock
T-regulatory (Treg) cells are like other cells present throughout the body in being subject to biochemical modifications in response to extracellular signals. An important component of these responses involves changes in post-translational modifications (PTMs) of histones and many non-histone proteins, including phosphorylation/dephosphorylation, ubiquitination/deubiquitination and acetylation/deacetylation. Foxp3, the key transcription factor of Tregs, is constantly being rapidly turned over, and a number of these PTMs determine its level of expression and activity...
March 30, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29582477/immune-molecular-profiling-of-whole-blood-drawn-from-a-non-human-primate-cardiac-xenograft-model-treated-with-anti-cd154-monoclonal-antibodies
#16
Sun A Ock, Keon Bong Oh, Seongsoo Hwang, Ik Jin Yun, Curie Ahn, Hyun Ken Chee, Hwajung Kim, Imran Ullah, Gi-Sun Im, Eung Woo Park
Most studies of xenografts have been carried out with complex immunosuppressive regimens to prevent immune rejection; however, such treatments may be fatal owing to unknown causes. Here, we performed immune molecular profiling following anti-CD154 monoclonal antibody (mAb) treatment in heterotopic abdominal cardiac xenografts from α-1,3-galactosyltransferase-knockout pigs into cynomolgus monkeys to elucidate the mechanisms mediating the undesirable fatal side effects of immunosuppressive agents. Blood samples were collected from healthy monkeys as control and then at 2 days after xenograft transplantation and just before humane euthanasia; 94 genes related to the immune system were analyzed...
March 26, 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29579824/peripheral-blood-regulatory-t-cells-are-diminished-in-kidney-transplant-patients-with-chronic-allograft-nephropathy
#17
M A Carmona-Escamilla, G Queipo, L A García-Mosqueda, L García-Covarrubias, M A Fonseca-Sánchez, E Villanueva-Ortega, P Prieto, R Lascurain
BACKGROUND: Our aim in this study was to assess peripheral blood CD4+ CD25+ FOXP3+ regulatory T cell (Treg) levels in patients with chronic allograft nephropathy (CAN) 1 year after kidney transplantation. METHODS: Twelve renal transplant patients with an initial onset of CAN, 12 patients with chronic kidney disease (CKD) stage G5 on dialysis, and 13 healthy control individuals were evaluated regarding the proportion of Tregs in their peripheral blood via flow cytometry...
March 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29576879/the-balance-of-th1-th2-and-lap-tregs-th17-cells-is-crucial-for-graft-survival-in-allogeneic-corneal-transplantation
#18
Shang Li, Jing Yu, Chungang Guo, Ying Jie, Zhiqiang Pan
Purpose: CD4+LAP+ T cells are newly discovered regulatory T cells (Tregs). The aim of this study is to investigate the balance of Th1/Th2 and LAP+Tregs/Th17 in mice after allogeneic corneal transplantation. Methods: A total of 65 mice received orthotopic penetrating transplantation. According to the survival scores of the grafts, the mice were divided into the rejection group and the survival group 3 weeks after transplantation. Th1, Th2, Th17, and regulatory T cells in the ipsilateral drainage lymph nodes and spleens were measured with flow cytometry...
2018: Journal of Ophthalmology
https://www.readbyqxmd.com/read/29571601/high-circulating-cd4-cd25-hi-foxp3-t-cell-sub-population-early-after-lung-transplantation-is-associated-with-development-of-bronchiolitis-obliterans-syndrome
#19
Maxim Durand, Philippe Lacoste, Richard Danger, Lola Jacquemont, Carole Brosseau, Eugénie Durand, Gaelle Tilly, Jennifer Loy, Aurore Foureau, Pierre-Joseph Royer, Adrien Tissot, Antoine Roux, Martine Reynaud-Gaubert, Romain Kessler, Sacha Mussot, Claire Dromer, Olivier Brugière, Jean François Mornex, Romain Guillemain, Johanna Claustre, Nicolas Degauque, Antoine Magnan, Sophie Brouard
BACKGROUND: Chronic bronchiolitis obliterans syndrome (BOS) remains a major limitation for long-term survival after lung transplantation. The immune mechanisms involved and predictive biomarkers have yet to be identified. The purpose of this study was to determine whether peripheral blood T-lymphocyte profile could predict BOS in lung transplant recipients. METHODS: An in-depth profiling of CD4+ and CD8+ T cells was prospectively performed on blood cells from stable (STA) and BOS patients with a longitudinal follow-up...
March 20, 2018: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/29569981/regulatory-t-cells-within-bone-marrow-derived-stem-cells-actively-confer-immunomodulatory-and-neuroprotective-effects-against-stroke
#20
Elliot G Neal, Sandra A Acosta, Yuji Kaneko, Xunming Ji, Cesario V Borlongan
Regulatory T-cells (Tregs ) may exert a neuroprotective effect on ischemic stroke by inhibiting both inflammation and effector T-cell activation. Transplantation of human bone marrow-derived stem cells (BMSCs) in ischemic stroke affords neuroprotection that results in part from the cells' anti-inflammatory property. However, the relationship between Tregs and BMSCs in treatment of ischemic stroke has not been fully elucidated. Here, we tested the hypothesis that Tregs within the BMSCs represent active mediators of immunomodulation and neuroprotection in experimental stroke...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
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