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Foxp3 transplant

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https://www.readbyqxmd.com/read/28720146/analysis-of-long-term-cd4-cd25highcd127-t-reg-cells-kinetics-in-peripheral-blood-of-lung-transplant-recipients
#1
Davide Piloni, Monica Morosini, Sara Magni, Alice Balderacchi, Luigia Scudeller, Emanuela Cova, Tiberio Oggionni, Giulia Stella, Carmine Tinelli, Filippo Antonacci, Andrea Maria D'Armini, Federica Meloni
BACKGROUND: The role of CD4(+)CD25(high)CD127(-) T-reg cells in solid-organ Transplant (Tx) acceptance has been extensively studied. In previous studies on kidney and liver recipients, peripheral T-reg cell counts were associated to graft survival, while in lung Tx, there is limited evidence for similar findings. This study aims to analyze long term peripheral kinetics of T-reg-cells in a cohort of lung recipients and tests its association to several clinical variables. METHODS: From jan 2009 to dec 2014, 137 lung Tx recipients were submitted to an immunological follow up (median: 105...
July 18, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/28706983/preimplantation-kidney-biopsies-of-extended-criteria-donors-have-a-heavier-inflammatory-burden-than-kidneys-from-standard-criteria-donors
#2
Camila M Mazeti-Felicio, Heloisa C Caldas, Ida M M Fernandes-Charpiot, Camila Z Dezotti, Maria A S F Baptista, Mario Abbud-Filho
BACKGROUND: Donors after brain death develop a systemic proinflammatory state that may predispose the kidneys to injury after transplantation. Because it is not known whether this inflammatory environment similarly affects the kidneys from expanded criteria donor (ECD) and standard criteria donors (SCD), we sought to evaluate differences in the gene expression of inflammatory cytokines in preimplantation biopsies (PIBx) from ECD and SCD kidneys. METHODS: Cytokines gene expression was measured in 80 PIBx (SCD, 52; ECD, 28) and associated with donor variables...
July 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28702031/alloantigen-induced-regulatory-t-cells-generated-in-presence-of-vitamin-c-display-enhanced-stability-of-foxp3-expression-and-promote-skin-allograft-acceptance
#3
Eirini Nikolouli, Matthias Hardtke-Wolenski, Martin Hapke, Michael Beckstette, Robert Geffers, Stefan Floess, Elmar Jaeckel, Jochen Huehn
Regulatory T cells (Tregs) are critical for the maintenance of immune homeostasis and self-tolerance and can be therapeutically used for prevention of unwanted immune responses such as allotransplant rejection. Tregs are characterized by expression of the transcription factor Foxp3, and recent work suggests that epigenetic imprinting of Foxp3 and other Treg-specific epigenetic signatures genes is crucial for the stabilization of both Foxp3 expression and immunosuppressive properties within Tregs. Lately, vitamin C was reported to enhance the activity of enzymes of the ten-eleven translocation family, thereby fostering the demethylation of Foxp3 and other Treg-specific epigenetic signatures genes in developing Tregs...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28701508/prdm1-regulates-thymic-epithelial-function-to-prevent-autoimmunity
#4
Natalie A Roberts, Brian D Adams, Nicholas I McCarthy, Reuben M Tooze, Sonia M Parnell, Graham Anderson, Susan M Kaech, Valerie Horsley
Autoimmunity is largely prevented by medullary thymic epithelial cells (TECs) through their expression and presentation of tissue-specific Ags to developing thymocytes, resulting in deletion of self-reactive T cells and supporting regulatory T cell development. The transcription factor Prdm1 has been implicated in autoimmune diseases in humans through genome-wide association studies and in mice using cell type-specific deletion of Prdm1 in T and dendritic cells. In this article, we demonstrate that Prdm1 functions in TECs to prevent autoimmunity in mice...
July 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28690612/protection-of-mice-from-acute-graft-versus-host-disease-requires-cd28-co-stimulation-on-donor-cd4-foxp3-regulatory-t-cells
#5
Anna Uri, Sandra Werner, Fred Lühder, Thomas Hünig, Thomas Kerkau, Niklas Beyersdorf
Acute graft-versus-host disease (aGvHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell plus T cell transplantation (allo-HSCT). In this study, we investigated the requirement for CD28 co-stimulation of donor CD4(+) conventional (CD4(+)CD25(-)Foxp3(-), Tconv) and regulatory (CD4(+)CD25(+)Foxp3(+), Treg) T cells in aGvHD using tamoxifen-inducible CD28 knockout (iCD28KO) or wild-type (wt) littermates as donors of CD4(+) Tconv and Treg. In the highly inflammatory C57BL/6 into BALB/c allo-HSCT transplantation model, CD28 depletion on donor CD4(+) Tconv reduced clinical signs of aGvHD, but did not significantly prolong survival of the recipient mice...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28654060/functional-characterization-of-regulatory-macrophages-that-inhibit-graft-reactive-immunity
#6
Jordi Ochando, Patricia Conde
Macrophage accumulation in transplanted organs has long been recognized as a feature of allograft rejection(1). Immunogenic monocytes infiltrate the allograft early after transplantation, mount a graft reactive response against the transplanted organ, and initiate organ rejection(2). Recent data suggest that suppressive macrophages facilitate successful long-term transplantation(3) and are required for the induction of transplantation tolerance(4). This suggests a multidimensional concept of macrophage ontogeny, activation, and function, which demands a new roadmap for the isolation and analysis of macrophage function(5)...
June 7, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28652007/cytokines-affecting-cd4-t-regulatory-cells-in-transplant-tolerance-iii-interleukin-5-il-5-promotes-survival-of-alloantigen-specific-cd4-t-regulatory-cells
#7
Bruce M Hall, Karren M Plain, Giang T Tran, Nirupama D Verma, Catherine M Robinson, Masaru Nomura, Rochelle Boyd, Suzanne J Hodgkinson
CD4(+)T cells mediate antigen-specific allograft tolerance, but die in culture without activated lymphocyte derived cytokines. Supplementation of the media with cytokine rich supernatant, from ConA activated spleen cells, preserves the capacity of tolerant cells to transfer tolerance and suppress rejection. rIL-2 or rIL-4 alone are insufficient to maintain these cells, however. We observed that activation of naïve CD4(+)CD25(+)FOXP3(+)Treg with alloantigen and the Th2 cytokine rIL-4 induces them to express interleukin-5 specific receptor alpha (IL-5Rα) suggesting that IL-5, a Th2 cytokine that is produced later in the immune response may promote tolerance mediating Treg...
June 23, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28647182/preoperative-application-of-combination-of-portal-venous-injection-of-donor-spleen-cells-and-intraperitoneal-injection-of-rapamycin-prolongs-the-survival-of-cardiac-allografts-in-mice
#8
Wen-Lin Gong, Chuang Sha, Gang Du, Zhong-Gui Shan, Zhong-Quan Qi, Su-Fang Zhou, Nuo Yang, Yong-Xiang Zhao
OBJECTIVE: To investigate the effects of preoperative portal venous injection of donor spleen cells (PVIDSC) and intraperitoneal injection of rapamycin in the acute rejection of cardiac allograft in mice and the underlying mechanisms. METHODS: Homogenous female B6 mice and BALB/c mice were used as recipients and donors of heart transplantation. These mice were randomly divided into different groups and received PVIDSC alone, rapamycin alone, or PVIDSC and rapamycin combined therapy...
May 2017: Asian Pacific Journal of Tropical Medicine
https://www.readbyqxmd.com/read/28643491/association-of-foxp3-polymorphism-with-allograft-outcome-in-kidney-transplantation
#9
Hyewon Park, Nuri Lee, Ji Won In, Eun Youn Roh, Kyoung Un Park, Sue Shin, Jaeseok Yang, Eun Young Song
BACKGROUND: Forkhead box P3 (Foxp3) is the most reliable marker for regulatory T cells, which play an important role in maintaining renal allograft tolerance. Recently, Foxp3 polymorphisms have been reported to be associated with graft outcome in kidney transplantation. We analyzed the association of Foxp3 polymorphisms with renal allograft outcome. METHODS: Foxp3 polymorphisms (rs3761548 A/C, rs2280883 C/T, rs5902434 del/ATT, and rs2232365 A/G) were tested by PCR with sequence-specific primers (PCR-SSP) in 231 adult kidney transplantation recipients from 1996-2004 at Seoul National University Hospital...
September 2017: Annals of Laboratory Medicine
https://www.readbyqxmd.com/read/28638744/azacytidine-prevents-experimental-xenogeneic-graft-versus-host-disease-without-abrogating-graft-versus-leukemia-effects
#10
Grégory Ehx, Gilles Fransolet, Laurence de Leval, Stéphanie D'Hondt, Sophie Lucas, Muriel Hannon, Loïc Delens, Sophie Dubois, Pierre Drion, Yves Beguin, Stéphanie Humblet-Baron, Frédéric Baron
The demethylating agent 5-azacytidine (AZA) has proven its efficacy in the treatment of myelodysplastic syndrome and acute myeloid leukemia. In addition, AZA can demethylate FOXP3 intron 1 (FOXP3i1) leading to the generation of regulatory T cells (Treg). Here, we investigated the impact of AZA on xenogeneic graft-vs.-host disease (xGVHD) and graft-vs.-leukemia effects in a humanized murine model of transplantation (human PBMCs-infused NSG mice), and described the impact of the drug on human T cells in vivo...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28638110/a-novel-and-effective-method-to-generate-human-porcine-specific-regulatory-t-cells-with-high-expression-of-il-10-tgf-%C3%AE-1-and-il-35
#11
Mingqian Li, Judith Eckl, Christiane Geiger, Dolores J Schendel, Heike Pohla
Organ transplantation remains the most effective treatment for patients with late stage organ failure. Transgenic pigs provide an alternative organ donor source to the limited availability of human organs. However, cellular rejection still remains to be the obstacle for xenotransplantation. Superior to other methods, antigen-specific regulatory T cells (Treg) alleviate cellular rejection with fewer side effects. Here we demonstrate the use of a fast method to provide tolerogenic dendritic cells (tolDC) that can be used to generate effective porcine-specific Treg cells (PSTreg)...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28637803/protein-malnutrition-alters-tryptophan-and-angiotensin-converting-enzyme-2-homeostasis-and-adaptive-immune-responses-in-human-rotavirus-infected-gnotobiotic-pigs-transplanted-with-human-infant-fecal-microbiota
#12
David D Fischer, Sukumar Kandasamy, Francine C Paim, Stephanie N Langel, Moyasar A Alhamo, Lulu Shao, Juliet Chepngeno, Ayako Miyazaki, Huang-Chi Huang, Anand Kumar, Gireesh Rajashekara, Linda J Saif, Anastasia N Vlasova
Malnutrition leads to increased morbidity and is evident in almost half of all deaths in children under the age of five. Mortality due to rotavirus diarrhea is common in developing countries where malnutrition is prevalent; however, the relationship between malnutrition and rotavirus infection remains unclear. In this study, gnotobiotic pigs transplanted with the fecal microbiota of a healthy 2-month-old infant were fed protein-sufficient or -deficient diets with infected with virulent human rotavirus. After human rotavirus infection, protein deficient pigs had decreased human rotavirus antibody titers and total IgA concentrations, systemic T helper (CD3+CD4+) and cytotoxic T (CD3+CD8+) lymphocyte frequencies and serum tryptophan and angiotensin I converting enzyme 2...
June 21, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28623282/a-nationwide-study-of-severe-and-protracted-diarrhoea-in-patients-with-primary-immunodeficiency-diseases
#13
Wen-I Lee, Chien-Chang Chen, Tang-Her Jaing, Liang-Shiou Ou, Chuen Hsueh, Jing-Long Huang
Diarrhoea lasting longer than 14 days and failing to respond to conventional management is defined as severe and protracted diarrhoea (SD). In this study, we investigated the prevalence, pathogens and prognosis of SD in primary immunodeficiency diseases (PIDs). Among 246 patients with predominantly paediatric-onset PIDs from 2003-2015, 21 [Btk (six), IL2RG (four), WASP, CD40L, gp91 (three each), gp47, RAG2 (one each)] and five [CVID (four), SCID (one)] without identified mutations had SD before prophylactic treatment...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28620237/lea29y-expression-in-transgenic-neonatal-porcine-islet-like-cluster-promotes-long-lasting-xenograft-survival-in-humanized-mice-without-immunosuppressive-therapy
#14
L Wolf-van Buerck, M Schuster, F S Oduncu, A Baehr, T Mayr, S Guethoff, J Abicht, B Reichart, N Klymiuk, E Wolf, J Seissler
Genetically engineered pigs are a promising source for islet cell transplantation in type 1 diabetes, but the strong human anti-pig immune response prevents its successful clinical application. Here we studied the efficacy of neonatal porcine islet-like cell clusters (NPICCs) overexpressing LEA29Y, a high-affinity variant of the T cell co-stimulation inhibitor CTLA-4Ig, to engraft and restore normoglycemia after transplantation into streptozotocin-diabetic NOD-SCID IL2rγ(-/-) (NSG) mice stably reconstituted with a human immune system...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28619045/human-adipose-derived-mesenchymal-stem-cells-alleviate-obliterative-bronchiolitis-in-a-murine-model-via-ido
#15
Guoping Zheng, Guanguan Qiu, Menghua Ge, Jianping He, Lanfang Huang, Ping Chen, Wei Wang, Qi Xu, Yaoqin Hu, Qiang Shu, Jianguo Xu
BACKGROUND: Long-term survival of lung transplantation is hindered by the development of obliterative bronchiolitis (OB). Adipose-derived stem cells (ASCs) were documented to have more potent immunosuppressive ability than mesenchymal stem cells (MSCs) from bone marrow and placenta. The goal of our study is to evaluate the effect of repeated administration of ASCs on OB and the involvement of indoleamine 2,3-dioxygenase (IDO) mediating the protective effect of ASCs in a heterotopic tracheal transplantation (HTT) model...
June 15, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28608637/regulatory-t-cell-therapy-in-liver-transplantation
#16
REVIEW
Gavin P Whitehouse, Andrew Hope, Alberto Sanchez-Fueyo
Modern immunosuppression drug regimens have produced excellent short term survival after liver transplantation but it is generally accepted that the side effects of these medications remain a significant contributing factor for less satisfactory long term outcomes. The liver has unique tolerogenic properties as evidenced by the higher rates of operational tolerance seen in liver transplant recipients compared to other solid organ transplants and therefore liver transplantation offers an attractive setting in which to study tolerising therapies...
June 13, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28600182/mesenchymal-stem-cells-can-induce-regulatory-t-cells-via-modulating-mir-126a-but-not-mir-10a
#17
Maryam Khosravi, Mohammad Hossein Karimi, Mahdokht Hossein Aghdaie, Mehdi Kalani, Sina Naserian, Ali Bidmeshkipour
Among the different immunosuppressive properties attributed to mesenchymal stem cells (MSCs), one relies on their ability to induce regulatory T cells (iTregs) from conventional T cells under particular inflammatory context. Stable Foxp3 expression plays a major role in the phenotypic and functional stability of iTregs. However, the mechanism behind Foxp3 induction in iTregs by MSCs remains unknown. Here, we assessed the possible effect of MSCs on miR-126a and miR-10a expression in iTregs and, consequently on Foxp3 stability, a regulatory pathway that has not yet been explored...
June 18, 2017: Gene
https://www.readbyqxmd.com/read/28590550/osi-027-modulates-acute-graft-versus-host-disease-after-liver-transplantation-in-a-rat-model
#18
Xiao Zhi, Fei Xue, Wei Chen, Chao Liang, Hao Liu, Tao Ma, Xuefeng Xia, Liqiang Hu, Xueli Bai, Tingbo Liang
Despite its rarity (1%-2%), acute graft-versus-host disease after liver transplantation (LTx-aGVHD) has a high mortality rate (85%). A gradual decrease in regulatory T cells (T-regs) correlates with disease progression in a rat LTx-GVHD model and treatments which increase T-regs exert therapeutic effects on LTx-aGVHD. In this study, LTx-aGVHD model rats were treated with rapamycin (RAPA), OSI-027 or an equal quantity of vehicle. Rats treated with OSI-027 survived longer (>100 days) than those in the RAPA (70±8 days) or control (24±3 days) groups...
June 7, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28584086/il-2-therapy-restores-regulatory-t-cell-dysfunction-induced-by-calcineurin-inhibitors
#19
Gavin Whitehouse, Elizabeth Gray, Sotiris Mastoridis, Elliot Merritt, Elisavet Kodela, Jennie H M Yang, Richard Danger, Marta Mairal, Sofia Christakoudi, Juan J Lozano, Iain C Macdougall, Timothy I M Tree, Alberto Sanchez-Fueyo, Marc Martinez-Llordella
CD4(+)CD25(+)FOXP3(+) Tregs constitute a heterogeneous lymphocyte subpopulation essential for curtailing effector T cells and establishing peripheral tolerance. Calcineurin inhibitors (CNIs) are among the most effective agents in controlling effector T-cell responses in humans. However, CNIs also reduce the size of the Treg pool. The functional consequences of this negative effect and the mechanisms responsible remain to be elucidated. We report here that CNIs compromise the overall Treg immunoregulatory capacity to a greater extent than would be predicted by the reduction in the size of the Treg compartment, given that they selectively promote the apoptosis of the resting and activated Treg subsets that are known to display the most powerful suppressive function...
July 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28562677/correction-helios-expression-and-foxp3-tsdr-methylation-of-ifny-and-ifny-treg-from-kidney-transplant-recipients-with-good-long-term-graft-function
#20
Karina Trojan, Christian Unterrainer, Rolf Weimer, Nuray Bulut, Christian Morath, Mostafa Aly, Li Zhu, Gerhard Opelz, Volker Daniel
[This corrects the article DOI: 10.1371/journal.pone.0173773.].
2017: PloS One
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