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Foxp3 transplant

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https://www.readbyqxmd.com/read/28434942/ipsc-derived-regulatory-dendritic-cells-inhibit-allograft-rejection-by%C3%A2-generating-alloantigen-specific-regulatory-t-cells
#1
Songjie Cai, Jiangang Hou, Masayuki Fujino, Qi Zhang, Naotsugu Ichimaru, Shiro Takahara, Ryoko Araki, Lina Lu, Ji-Mei Chen, Jian Zhuang, Ping Zhu, Xiao-Kang Li
Regulatory dendritic cell (DCregs)-based immunotherapy is a potential therapeutic tool for transplant rejection. We generated DCregs from murine induced pluripotent stem cells (iPSCs), which could remain in a "stable immature stage" even under strong stimulation. Harnessing this characteristic, we hypothesized that iPS-DCregs worked as a negative vaccine to generate regulatory T cells (Tregs), and induced donor-specific allograft acceptance. We immunized naive CBA (H-2K(k)) mice with B6 (H-2K(b)) iPS-DCregs and found that Tregs (CD4(+)CD25(+)FOXP3(+)) significantly increased in CBA splenocytes...
April 18, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28420440/immune-response-after-autologous-hematopoietic-stem-cell-transplantation-in-type-1-diabetes-mellitus
#2
Lei Ye, Li Li, Bing Wan, Minglan Yang, Jie Hong, Weiqiong Gu, Weiqing Wang, Guang Ning
BACKGROUND: This study explored the details of the immune response after autologous hematopoietic stem cell transplantation (AHSCT) treatment in type 1 diabetes mellitus. METHODS: Peripheral blood mononuclear cells (PBMCs) from 18 patients with type 1 diabetes mellitus were taken at baseline and 12 months after AHSCT or insulin-only therapy. The lymphocyte proliferation, mRNA expression and secretion of pro-inflammatory and anti-inflammatory cytokines belonging to T-helper type 1 (Th1), T-helper type 17 (Th17) and regulatory T (Treg) cells in PBMC culture supernatants were assessed...
April 18, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28415767/unique-properties-of-thymic-antigen-presenting-cells-promote-epigenetic-imprinting-of-alloantigen-specific-regulatory-t-cells
#3
Garima Garg, Eirini Nikolouli, Matthias Hardtke-Wolenski, Aras Toker, Naganari Ohkura, Michael Beckstette, Takahisa Miyao, Robert Geffers, Stefan Floess, Norbert Gerdes, Esther Lutgens, Anke Osterloh, Shohei Hori, Shimon Sakaguchi, Elmar Jaeckel, Jochen Huehn
Regulatory T cells (Tregs) are potential immunotherapeutic candidates to induce transplantation tolerance. However, stability of Tregs still remains contentious and may potentially restrict their clinical use. Recent work suggested that epigenetic imprinting of Foxp3 and other Treg-specific signature genes is crucial for stabilization of immunosuppressive properties of Foxp3+ Tregs, and that these events are initiated already during early stages of thymic Treg development. However, the mechanisms governing this process remain largely unknown...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28403126/effector-antitumor-and-regulatory-t-cell-responses-influence-the-development-of-nonmelanoma-skin-cancer-in-kidney-transplant-patients
#4
Elena Crespo, Loreto Fernandez, Marc Lúcia, Edoardo Melilli, Ricardo Lauzurica, Rosa Maria Penin, Ariadna Quer, Sergio Luque, Maria Quero, Anna Manonelles, Joan Torras, Josep Maria Cruzado, Laura Cañas, Josep Maria Grinyó, Oriol Bestard
BACKGROUND: Chronic immunosuppression promotes Nonmelanocytic Squamous Cell Carcinoma (SCC) after kidney transplantation. Adaptive and innate immunity play a key role controlling tumor growth and are influenced by different immunosuppressive agents. We hypothesized that functional impairment of tumor-specific T cell responses due to CNI could contribute to SCC development, whereas conversion to mTOR-i could recover this protective immune response. METHODS: Peripheral tumor-specific T cell responses against main SCC-derived antigens using the IFN-γ ELISPOT assay and intratumor and circulating immune phenotypes (CD4+T, CD8+T, CD20+B, CD56+NK, FOXP3+Tregs) were explored in a cross-sectional analysis in 59 kidney transplant patients with SCC on CNI (KT-CNI-SCC) or mTOR-i (KT-mTORi-SCC), 25 nontransplants developing SCC (NoKT-SCC) and 6 healthy controls...
April 11, 2017: Transplantation
https://www.readbyqxmd.com/read/28389319/in-vitro-immunoregulatory-effects-of-thymoglobulin-on-human-immune-cell-subpopulations
#5
Maja Buszko, Bojana Jakic, Christian Ploner, Paul Hoertnagl, Christina Mayerl, Georg Wick, Giuseppe Cappellano
Thymoglobulin (ATG) is a polyclonal rabbit antibody against human thymocytes used as a T cell-depleting agent in organ transplantation. Its polyclonal character suggests that its effect may go far beyond just T cell depletion. The aim of this study was to further elucidate possible mechanisms underlying the suppressive activity of ATG. For in vitro studies, human peripheral blood mononuclear cells (PBMC) were incubated with ATG or control Ig for various time points. Foxp3(+) regulatory cells (Tregs) and monocytes were phenotypically analyzed by flow cytometry and functionally tested by in vitro suppression assays...
April 4, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28379122/recipient-adipose-derived-stem-cells-enhance-recipient-cell-engraftment-and-prolong-allotransplant-survival-in-a-miniature-swine-hind-limb-model
#6
Yur-Ren Kuo, Chien-Chang Chen, Yen-Chou Chen, Ching-Ming Chien
Donor mesenchymal stem cells could prolong vascularized composite allotransplant (VCA) survival in our previous study.However, recipient adipose tissue is easier to harvest than donor tissue for pre-conditioning modulation. Hence, this study investigated the efficacy of recipient autologous adipose-derived stem cells (rASCs) for VCA survival. The heterotopic hind-limb transplantation from female donor to male recipient was performed in out-bred miniature swine. Group-I (N=6) were untreated controls. Group-II (N=4) obtained rASC infusions (given on week 0, +1, +2, and +3)...
March 17, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28372951/disturbances-in-iron-homeostasis-result-in-accelerated-rejection-after-experimental-heart-transplantation
#7
Thomas Resch, Muhammad Imtiaz Ashraf, Paul Viktor Ritschl, Susanne Ebner, Cornelia Fabritius, Andrea Brunner, Georg Schäfer, Heinz Regele, Julia Günther, Günter Weiss, Katja Kotsch
BACKGROUND: Clinical data suggest that iron disturbances deleteriously affect graft survival after heart transplantation (HTx), but immunological mechanisms underlying this phenomenon have not yet been elucidated. METHODS: To identify the mechanistic influence of iron in a murine model of HTx, fully allogeneic BALB/c donor organs were transplanted into iron-overloaded or iron-deficient C57BL/6 mice, and recipients were analyzed for functional and immunological parameters...
March 7, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28351935/bidirectional-immune-tolerance-in-non-myeloablative-mhc-mismatched-bmt-for-murine-%C3%AE-thalassemia
#8
Shuyu E, Aman Seth, Peter Vogel, Matt Sommers, Taren Ong, Asha B Pillai
Non-myeloablative conditioning using total lymphoid irradiation (TLI) and rabbit anti-thymocyte serum (ATS) (the murine pre-clinical equivalent of anti-thymocyte globulin/ATG) facilitates immune tolerance after bone marrow transplantation (BMT) across major histocompatibility complex (MHC) disparities and may be a useful strategy for non-malignant disorders. We previously reported that donor effector T cell function and GVHD are regulated via recipient invariant natural killer T cell (iNKT cell) IL-4-driven expansion of donor Foxp3(+) naturally occurring Treg...
March 28, 2017: Blood
https://www.readbyqxmd.com/read/28345003/expansion-of-human-tregs-from-cryopreserved-umbilical-cord-blood-for-gmp-compliant-autologous-adoptive-cell-transfer-therapy
#9
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/28337956/acute-renal-graft-versus-host-disease-in-a-murine-model-of-allogeneic-bone-marrow-transplantation
#10
Peter M Schmid, Abdellatif Bouazzaoui, Karin Schmid, Christoph Birner, Christian Schach, Lars S Maier, Ernst Holler, Dierk H Endemann
Acute kidney injury (AKI) is a very common complication after allogeneic bone marrow transplantation (BMT) and associated with poor prognosis. Generally kidneys are assumed to be no direct target of Graft-versus-Host Disease (GvHD), and renal impairment is often attributed to several other factors occurring in the early phase after BMT. Our study aimed to prove the existence of renal GvHD in a fully MHC-mismatched model of BALB/c mice conditioned and transplanted according to two different intensity protocols...
March 23, 2017: Cell Transplantation
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
#11
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...
March 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28324830/chitinase-3-like-1-deficient-donor-splenocytes-accentuated-the-pathogenesis-of-acute-graft-versus-host-diseases-through-regulating-t-cell-expansion-and-type-i-inflammation
#12
Zengyao Li, Jian Gu, Jing Liu, Qin Zhu, Hao Lu, Yunjie Lu, Jianhua Rao, Ling Lu, Xuehao Wang
Acute graft-versus-host disease (aGVHD) is a major complication following transplantation, limiting the success of this therapy. Chitinase 3-like-1 (CHI3L1), a member of the glycosyl hydrolase 18 family, plays a critical role in bacterial infections, allergic disease and a variety of malignancies. Here, we investigated whether CHI3L1 could affect the pathogenesis of aGVHD in a mouse allo-HCT model. In this study, we show that CHI3L1 deficiency in donor T cells increased the severity of aGVHD through enhancing systemic and local inflammation...
May 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28321218/the-induction-and-maintenance-of-transplant-tolerance-engages-both-regulatory-and-anergic-cd4-t-cells
#13
Alix Besançon, Marije Baas, Tania Goncalves, Fabrice Valette, Herman Waldmann, Lucienne Chatenoud, Sylvaine You
Therapeutic tolerance to self-antigens or foreign antigens is thought to depend on constant vigilance by Foxp3(+) regulatory T cells (Tregs). Previous work using a pancreatic islet allograft model and a short pulse of CD3 antibody therapy has shown that CD8(+) T cells become anergic and use TGFβ and coinhibitory signaling as their contribution to the tolerance process. Here, we examine the role of CD4(+) T cells in tolerization by CD3 antibodies. We show that both Foxp3(+) Tregs and CD4(+) T cell anergy play a role in the induction of tolerance and its maintenance...
2017: Frontiers in Immunology
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
#14
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/28302753/erythropoietin-receptor-mediated-molecular-crosstalk-promotes-t-cell-immunoregulation-and-transplant-survival
#15
Carolina Purroy, Robert L Fairchild, Toshiaki Tanaka, William M Baldwin, Joaquin Manrique, Joren C Madsen, Robert B Colvin, Alessandro Alessandrini, Bruce R Blazar, Miguel Fribourg, Chiara Donadei, Umberto Maggiore, Peter S Heeger, Paolo Cravedi
Although spontaneous kidney transplant acceptance/tolerance occurs in mice and occasionally in humans, mechanisms remain unclear. Herein we test the hypothesis that EPO, a hormone predominantly produced by the adult kidney, has immunomodulating properties that are required for spontaneous kidney graft acceptance. In vitro, in a manner dependent on the EPO receptor and CD131 on antigen-presenting cells, EPO induced the secretion of active TGFβ by antigen-presenting cells, which in turn converted naïve CD4(+) T cells into functional Foxp3(+) regulatory T cells (Treg)...
March 16, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28302215/-altered-treg-and-il-1a-expression-in-the-immune-microenvironment-%C3%A2-of-lung-squamous-cell-cancer-after-egfr-blockade
#16
Haiyang He, Luyu Qi, Yiling Hou
BACKGROUND: Targeting the mutations and amplifications in the epidermal growth factor receptor (EGFR) gene has curative effects on cancers of the lung, oral cavity, and gastrointestinal system. However, a systemic immune inflammation is an adverse effect of this therapeutic strategy. In this study, we aimed to identify the possible changes in the tumor microenvironment that contribute to the anti-cancer activity of EGFR inhibition. METHODS: Squamous-cell cancers were induced by the syngeneic transplantation of either EGFR-null or wild-type mouse primary keratinocytes that had been transduced with an oncogenic H-ras retrovirus...
March 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28296931/helios-expression-and-foxp3-tsdr-methylation-of-ifny-and-ifny-treg-from-kidney-transplant-recipients-with-good-long-term-graft-function
#17
Karina Trojan, Christian Unterrainer, Rolf Weimer, Nuray Bulut, Christian Morath, Mostafa Aly, Li Zhu, Gerhard Opelz, Volker Daniel
BACKGROUND: There is circumstantial evidence that IFNy+ Treg might have clinical relevance in transplantation. IFNy+ Treg express IFNy receptors and are induced by IFNy. In the present study we investigated in kidney transplant recipients with good long-term stable graft function the absolute cell counts of IFNy+ Treg subsets and whether their expression of Foxp3 is stable or transient. METHOD: Helios expression determined by eight-color-fluorescence flow cytometry and methylation status of the Foxp3 Treg specific demethylation region (TSDR) served as indicators for stability of Foxp3 expression...
2017: PloS One
https://www.readbyqxmd.com/read/28289675/humoral-immunodeficiency-with-hypotonia-feeding-difficulties-enteropathy-and-mild-eczema-caused-by-a-classical-foxp3-mutation
#18
Paul Tuijnenburg, Eloy Cuadrado, Annet M Bosch, Angelika Kindermann, Machiel H Jansen, Marielle Alders, Ester M M van Leeuwen, Taco W Kuijpers
We describe here the case of a boy who presented with pulmonary infections, feeding difficulties due to velopharyngeal insufficiency and gastroesophageal reflux, myopathy, and hypotonia soon after birth. Later, he was also found to have an elevated immunoglobulin (Ig) E and mild eczema and was diagnosed with inflammatory bowel disease. Further immunological screening at the age of 7 years showed low B and NK cell numbers but normal CD4(+) and CD8(+) T cells and notably, normal numbers of CD4(+) regulatory T (Treg) cells...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/28270810/a-novel-model-on-dst-induced-transplantation-tolerance-by-the-transfer-of-self-specific-donor-ttregs-to-a-haplotype-matched-organ-recipient
#19
Angelica Maria Mohr Gregoriussen, Henrik Georg Bohr
Donor-specific blood transfusion (DST) can lead to significant prolongation of allograft survival in experimental animal models and sometimes human recipients of solid organs. The mechanisms responsible for the beneficial effect on graft survival have been a topic of research and debate for decades and are not yet fully elucidated. Once we discover how the details of the mechanisms involved are linked, we could be within reach of a procedure making it possible to establish donor-specific tolerance with minimal or no immunosuppressive medication...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28258292/immunoregulatory-properties-of-the-cytokine-il-34
#20
REVIEW
Carole Guillonneau, Séverine Bézie, Ignacio Anegon
Interleukin-34 is a cytokine with only partially understood functions, described for the first time in 2008. Although IL-34 shares very little homology with CSF-1 (CSF1, M-CSF), they share a common receptor CSF-1R (CSF-1R) and IL-34 has also two distinct receptors (PTP-ζ) and CD138 (syndecan-1). To make the situation more complex, IL-34 has also been shown as pairing with CSF-1 to form a heterodimer. Until now, studies have demonstrated that this cytokine is released by some tissues that differ to those where CSF-1 is expressed and is involved in the differentiation and survival of macrophages, monocytes, and dendritic cells in response to inflammation...
March 3, 2017: Cellular and Molecular Life Sciences: CMLS
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