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Foxp3 transplant

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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
#1
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
#2
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...
March 16, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28321218/the-induction-and-maintenance-of-transplant-tolerance-engages-both-regulatory-and-anergic-cd4-t-cells
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/28251801/origin-of-enriched-regulatory-t-cells-in-patients-receiving-combined-kidney-bone-marrow-transplantation-to-induce-transplantation-tolerance
#11
Ben Sprangers, Susan DeWolf, Thomas M Savage, Tatsuaki Morokata, Aleksandar Obradovic, Samuel A LoCascio, Brittany Shonts, Julien Zuber, Sai Ping Lau, Ravi Shah, Heather Morris, Valeria Steshenko, Emmanuel Zorn, Frederic I Preffer, Sven Olek, David M Dombkowski, Laurence A Turka, Robert Colvin, Robert Winchester, Tatsuo Kawai, Megan Sykes
We examined tolerance mechanisms in patients receiving HLA-mismatched combined kidney and bone marrow transplantation (CKBMT) that led to transient chimerism under a previously-published non-myeloablative conditioning regimen (Immune Tolerance Network study ITN036). Polychromatic flow cytometry (FCM) and high throughput sequencing of TCRβ hypervariable regions of DNA from peripheral blood T regulatory cells (Tregs) and CD4 non-Tregs revealed marked early enrichment of regulatory T cells (CD3(+) CD4(+) CD25(high) CD127(low) Foxp3(+) ) in blood that resulted from peripheral proliferation (Ki67(+) ), possibly new thymic emigration (CD31(+) ) and, in one tolerant subject, conversion from non-Tregs...
March 1, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28223693/single-cd28-stimulation-induces-stable-and-polyclonal-expansion-of-human-regulatory-t-cells
#12
Xuehui He, Ruben L Smeets, Esther van Rijssen, Annemieke M H Boots, Irma Joosten, Hans J P M Koenen
CD4+FOXP3+ Treg are essential for immune tolerance. Phase-1 clinical trials of Treg-therapy to treat graft-versus-host-disease reported safety and potential therapeutic efficacy. Treg-based trials have started in organ-transplant patients. However, efficient ex vivo expansion of a stable Treg population remains a challenge and exploring novel ways for Treg expansion is a pre-requisite for successful immunotherapy. Based on the recent finding that CD28-signaling is crucial for survival and proliferation of mouse Treg, we studied single-CD28 stimulation of human Treg, without T cell receptor stimulation...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28198408/therapeutic-effects-of-human-adipose-tissue-derived-stem-cell-hadsc-transplantation-on-experimental-autoimmune-encephalomyelitis-eae-mice
#13
Jia Li, Ying Chen, Zhibo Chen, Yuanyuan Huang, Dehao Yang, Zhongqian Su, Yiyun Weng, Xiang Li, Xu Zhang
This study is to investigate the therapeutic effects of human adipose tissue-derived stem cell (hADSC) transplantation on experimental autoimmune encephalomyelitis (EAE) in mice. EAE mouse model was established by MOG35-55 immunization. Body weight and neurological function were assessed. H&E and LFB staining was performed to evaluate histopathological changes. Flow cytometry was used to detect Th17 and Treg cells. ELISA and real-time PCR were performed to determine transcription factor and pro-inflammatory cytokine levels...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28195151/in-patients-with-chronic-aplastic-anemia-bone-marrow-derived-mscs-regulate-the-treg-th17-balance-by-influencing-the-notch-rbp-j-foxp3-ror%C3%AE-t-pathway
#14
Hongbo Li, Lin Wang, Yan Pang, Zujun Jiang, Zenghui Liu, Haowen Xiao, Haijia Chen, Xiaohu Ge, Hai Lan, Yang Xiao
The standard treatment for aplastic anemia (AA) in young patients is a matched sibling hematopoietic stem cell transplant. Transfusion of a chronic AA patient with allogeneic bone marrow-derived mesenchymal stromal cells (BMMSCs) is currently being developed as a cell-based therapy, and the safety and efficacy of such transfusions are being continuously improved. Nevertheless, the mechanisms by which BMMSCs exert their therapeutic effects remain to be elucidated. In this study, mesenchymal stromal cells (MSCs) obtained from bone marrow donors were concentrated and intravenously injected into 15 chronic AA patients who had been refractory to prior immunosuppressive therapy...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28194759/association-of-peripheral-nk-cell-counts-with-helios-ifny-tregs-in-patients-with-good-long-term-renal-allograft-function
#15
Karina Trojan, Li Zhu, Mostafa Aly, Rolf Weimer, Nuray Bulut, Christian Morath, Gerhard Opelz, Volker Daniel
BACKGROUND: Little is known about a possible interaction of NK cells with Tregs in long-term stable kidney transplant recipients. METHODS: Absolute counts of lymphocyte and Treg subsets were studied in whole blood samples of 136 long-term stable renal transplant recipients and 52 healthy controls using eight-color-fluorescence flow cytometry. Patients were 1946±2201 days (153-10268 days) posttransplant and showed a serum creatinine of 1.7±0.7 mg/dl. RESULTS: Renal transplant recipients investigated >1...
February 14, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28194440/transient-antibody-targeting-of-cd45rc-induces-transplant-tolerance-and-potent-antigen-specific-regulatory-t-cells
#16
Elodie Picarda, Séverine Bézie, Laetitia Boucault, Elodie Autrusseau, Stéphanie Kilens, Dimitri Meistermann, Bernard Martinet, Véronique Daguin, Audrey Donnart, Eric Charpentier, Laurent David, Ignacio Anegon, Carole Guillonneau
Rat and human CD4(+) and CD8(+) Tregs expressing low levels of CD45RC have strong immunoregulatory properties. We describe here that human CD45 isoforms are nonredundant and identify distinct subsets of cells. We show that CD45RC is not expressed by CD4(+) and CD8(+) Foxp3(+) Tregs, while CD45RA/RB/RO are. Transient administration of a monoclonal antibody (mAb) targeting CD45RC in a rat cardiac allotransplantation model induced transplant tolerance associated with inhibition of allogeneic humoral responses but maintained primary and memory responses against cognate antigens...
February 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28187014/delayed-donor-bone-marrow-infusion-induces-liver-transplant-tolerance
#17
Yan Xie, Yang Wu, Kang Xin, Jiao-Jing Wang, Hong Xu, Suzanne T Ildstad, Joseph Leventhal, Guang-Yu Yang, Zheng Zhang, Josh Levitsky
BACKGROUND: Nonmyeloablative conditioning followed by donor bone marrow infusion (BMI) to induce tolerance has not been robustly tested in liver transplantation (LT) and may be unsafe at the time of LT. We hypothesized T cell depleted BMI is effective in inducing tolerance when delayed after LT, resulting in potentially safer future clinical applications. METHODS: Nonimmunosuppressed syngeneic (Lewis to Lewis) and allogeneic (ACI to Lewis) rat LT transplants were initially performed as controls...
February 10, 2017: Transplantation
https://www.readbyqxmd.com/read/28176947/silencing-of-foxp3-enhances-the-antitumor-efficacy-of-gm-csf-genetically-modified-tumor-cell-vaccine-against-b16-melanoma
#18
Antonio Miguel, Luis Sendra, Verónica Noé, Carles J Ciudad, Francisco Dasí, David Hervas, María José Herrero, Salvador F Aliño
The antitumor response after therapeutic vaccination has a limited effect and seems to be related to the presence of T regulatory cells (Treg), which express the immunoregulatory molecules CTLA4 and Foxp3. The blockage of CTLA4 using antibodies has shown an effective antitumor response conducing to the approval of the human anti-CTLA4 antibody ipilimumab by the US Food and Drug Administration. On the other hand, Foxp3 is crucial for Treg development. For this reason, it is an attractive target for cancer treatment...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28162154/-the-effect-of-semimature-dendritic-cell-and-the-levels-of-treg-on-transplantation-tolerance-of-hepatocytes-differentiated-from-mouse-embryonic-stem-cell
#19
C Zhang, W W Liao, B Cai, F R Liu, Q Ke, X F Zhu, X S He, A B Hu
Objective: To investigate the inducing effect and mechanism of semimature dendritic cell (smDCs) on transplantation tolerance of hepatocytes differentiated from mouse embryonic stem cells (ESCs), and to study the connections between smDCs and regulatory dendritic cells (regDCs). Methods: ESCs of 129 mouse labelled green fluorescent protein (GFP) were induced to hepatocytes by using previous methods. Meanwhile, bone marrow mononuclear cells of 129 mouse were induced to smDCs and regDCs. Moreover, the hepatocytes differentiated from 129 mouse ESCs were transplanted into liver of BALB/c mouse 3 days after infusing smDCs and regDCs suspension of 129 mouse into BALB/c mouse by tail vein respectively...
January 24, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28161606/the-absolute-number-of-regulatory-t-cells-in-unmanipulated-peripheral-blood-grafts-predicts-the-occurrence-of-acute-graft-versus-host-disease-post-haplo-identical-hematopoietic-stem-cell-transplantation
#20
Li Ding, Heng Zhu, Yang Yang, Hong-Min Yan, Hai-Hong Zhang, Dong-Mei Han, Zhi-Dong Wang, Xiao-Li Zheng, Jing Liu, Ling Zhu, Mei-Xue, Zi-Kuan Guo, Heng-Xiang Wang
CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) have been reported to play a central role in suppressing acute graft-versus-host disease (aGVHD), but whether the Treg contents of grafts correlates with the occurrence of aGVHD post haplo-identical hematopoietic stem cell transplantation (haplo-HSCT) remains unclear. In the present study, changes in Tregs in peripheral blood (PB) were followed before and after granulocyte colony-stimulating factor (G-CSF) mobilization. In addition, functional analyses of Tregs in PB grafts and bone marrow (BM) grafts were performed...
January 18, 2017: Leukemia Research
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