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https://www.readbyqxmd.com/read/29316256/immunosuppressive-effect-of-the-gut-microbiome-altered-by-high-dose-tacrolimus-in-mice
#1
Z Zhang, L Liu, H Tang, W Jiao, S Zeng, Y Xu, Q Zhang, Z Sun, A Mukherjee, X Zhang, X Hu
The alterations induced in gut microbiota by tacrolimus may affect immune function and organ transplantation. Mice were treated with a high-dose of tacrolimus for 14 days. The fecal microbiota were analyzed by pyrosequencing the 16S rRNA genes, and the effect on metabolism was predicted using the sequence data. The subgroups of T cells in the serum, gut-associated lymphoid tissue and draining lymph nodes were determined by flow cytometry. Tacrolimus treatment significantly altered the relative abundance of Allobaculum, Bacteroides and Lactobacillus and CD4+ CD25hi FoxP3+ regulatory T-cells in the colonic mucosa and the circulation...
January 9, 2018: American Journal of Transplantation
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
#2
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/29250828/cd4-cd25hi-foxp3-regulatory-t-cells-in-long-term-cardiac-xenotransplantation
#3
Avneesh K Singh, Joshua L Chan, Caleb N Seavey, Philip C Corcoran, Robert F Hoyt, Billeta G T Lewis, Marvin L Thomas, David L Ayares, Keith A Horvath, Muhammad M Mohiuddin
BACKGROUND: CD4+CD25Hi FoxP3+ T (Treg) cells are a small subset of CD4+ T cells that have been shown to exhibit immunoregulatory function. Although the absolute number of Treg cells in peripheral blood lymphocytes (PBL) is very small, they play an important role in suppressing immune reactivity. Several studies have demonstrated that the number of Treg cells, rather than their intrinsic suppressive capacity, may contribute to determining the long-term fate of transplanted grafts. In this study, we analyzed Treg cells in PBL of long-term baboon recipients who have received genetically modified cardiac xenografts from pig donors...
December 17, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/29246938/ipilimumab-plus-lenalidomide-after-allogeneic-and-autologous-stem-cell-transplantation-for-patients-with-lymphoid-malignancies
#4
Issa F Khouri, Irina Fernandez Curbelo, Francesco Turturro, Elias Jabbour, Denai R Milton, Roland L Bassett, Luis Vence, James P Allison, Alison M Gulbis, Padmanee Sharma
PURPOSE: Prevention or treatment of relapsed lymphoid malignancies after hematopoietic stem cell transplantation (HSCT) requires novel strategies. We hypothesized that anti-tumor-cell responses could be enhanced by the addition of lenalidomide to the cytotoxic T-lymphocyte-associated protein 4 inhibitor ipilimumab. EXPERIMENTAL DESIGN: We conducted a phase 2 investigator-initiated trial to assess the safety and activity of ipilimumab and lenalidomide in patients with lymphoid malignancies that relapsed after allogeneic HSCT and in high-risk patients after autologous HSCT...
December 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29241729/long-term-follow-up-of-ipex-syndrome-patients-after-different-therapeutic-strategies-an-international-multicenter-retrospective-study
#5
Federica Barzaghi, Laura Cristina Amaya Hernandez, Benedicte Neven, Silvia Ricci, Zeynep Yesim Kucuk, Jack Bleesing, Zohreh Nademi, Mary Anne Slatter, Erlinda Rose Ulloa, Anna Shcherbina, Anna Roppelt, Austen Worth, Juliana Silva, Alessandro Aiuti, Luis Murguia-Favela, Carsten Speckmann, Magda Carneiro-Sampaio, Juliana Folloni Fernandes, Safa Baris, Ahmet Ozen, Elif Karakoc-Aydiner, Ayca Kiykim, Ansgar Schulz, Sandra Steinmann, Lucia Dora Notarangelo, Eleonora Gambineri, Paolo Lionetti, William Thomas Shearer, Lisa Forbes, Caridad Martinez, Despina Moshous, Stephane Blanche, Alain Fisher, Frank M Ruemmele, Come Tissandier, M Ouachee-Chardin, Frédéric Rieux-Laucat, Marina Cavazzana, Waseem Qasim, Barbarella Lucarelli, Michael H Albert, Ichiro Kobayashi, Laura Alonso, Cristina Diaz De Heredia, Hirokazu Kanegane, Anita Lawitschka, Jong Jin Seo, Marta Gonzalez-Vicent, Miguel Angel Diaz, Rakesh Kumar Goyal, Martin G Sauer, Akif Yesilipek, Minsoo Kim, Yesim Yilmaz-Demirdag, Monica Bhatia, Julie Khlevner, Erick J Richmond Padilla, Silvana Martino, Davide Montin, Olaf Neth, Agueda Molinos-Quintana, Justo Valverde-Fernandez, Arnon Broides, Vered Pinsk, Antje Ballauf, Filomeen Haerynck, Victoria Bordon, Catharina Dhooge, Maria Laura Garcia-Lloret, Robbert G Bredius, Krzysztof Kałwak, Elie Haddad, Markus Gerhard Seidel, Gregor Duckers, Sung-Yun Pai, Christopher C Dvorak, Stephan Ehl, Franco Locatelli, Frederick Goldman, Andrew Richard Gennery, Mort J Cowan, Maria Grazia Roncarolo, Rosa Bacchetta
BACKGROUND: Immunedysregulation Polyendocrinopathy Enteropathy X-linked (IPEX) syndrome is a monogenic autoimmune disease caused by FOXP3 mutations. Because it is a rare disease, the natural history and response to treatments, including allogeneic hematopoietic stem cell transplantation (HSCT) and immunosuppression (IS), have not been thoroughly examined. OBJECTIVE: To evaluate disease onset, progression and long-term outcome of the two main treatments in long-term IPEX survivors...
December 11, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29229400/tumor-necrosis-factor-producing-t-regulatory-cells-are-associated-with-severe-liver-injury-in-patients-with-acute-hepatitis-a
#6
Yoon Seok Choi, Min Kyung Jung, Jeewon Lee, Seong Jin Choi, Sung Hoon Choi, Hyun Woong Lee, Jong-Joo Lee, Hyung Joon Kim, Sang Hoon Ahn, Dong Hyeon Lee, Won Kim, Su-Hyung Park, Jun R Huh, Hyoung-Pyo Kim, Jun Yong Park, Eui-Cheol Shin
BACKGROUND AND AIMS: CD4+CD25+Foxp3+ T-regulatory (Treg) cells control immune responses and maintain immune homeostasis. However, under inflammatory conditions, Treg cells produce cytokines that promote inflammation. We investigated production of tumor necrosis factor (TNF) by Treg cells in patients with acute hepatitis A (AHA), and examined the characteristics of these cells and association with clinical factors. METHODS: We analyzed blood samples collected from 63 patients with AHA at the time of hospitalization (and some at later time points) and 19 healthy donors in South Korea...
December 8, 2017: Gastroenterology
https://www.readbyqxmd.com/read/29229149/transfusion-of-ethylene-carbodiimide-fixed-donor-splenocytes-prolongs-survival-of-vascularized-skin-allografts
#7
Jianke Ding, Shiqiang Liu, Dongliang Zhang, Yajuan Song, Xianjie Ma, Chenggang Yi, Baoqiang Song, Bo Xiao, Yingjun Su, Shuzhong Guo
BACKGROUND: Allograft rejection is a major obstacle to the widespread clinical application of vascularized composite allotransplantation. Recent studies revealed a noncytoreductive strategy to protect allografts by the transfusion of ethylene carbodiimide-fixed donor splenocytes (ECDI-SPs). To determine whether this approach offers advantages in protecting skin allografts, we examined the immunological protection of infusing ECDI-SPs with a 30-d administration of rapamycin on the skin allografts of mice...
January 2018: Journal of Surgical Research
https://www.readbyqxmd.com/read/29218089/the-role-of-sildenafil-in-the-development-of-transplant-arteriosclerosis-in-rat-aortic-grafts
#8
Shuai Luo, Mei Yang, Hao Jin, Zi-Qiang Xu, Yi-Fu Li, Peng Xia, Yi-Rrong Yang, Bi-Cheng Chen, Yan Zhang
Chronic rejection (CR), which is characterized histologically by progressive graft arteriosclerosis, remains a significant barrier to the long-term survival of a graft. Sildenafil has been shown to protect vascular endothelial cells. In this study, we found that sildenafil significantly reduces the thickness of transplant vascular intima in a rat aortic transplant model. Moreover, sildenafil dramatically decreased the expression of transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor (VEGF), and α-smooth muscle actin (α-SMA) in the grafted aortas and increased the concentrations of cyclic guanosine monophosphate (cGMP) and endothelial nitric oxide synthase (eNOS) in serum...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29210727/regulatory-t-cells-from-the-bench-to-the-clinic-and-back
#9
Basmah S Al Dulaijan, Amr Mansouri, Jordan Karnyski, Jamil Azzi
PURPOSE OF REVIEW: The main objective of this review is to briefly highlight how we gradually came to understand regulatory T cells (Tregs) and forkhead box p3 (FoxP3) biology, including their function and regulation. We will also discuss how this knowledge is being translated into the clinical setting and the significant challenges that need to be overcome. RECENT FINDINGS: CD4FoxP3 Tregs are key players in immune regulation. Their deficiency and dysfunction have been implicated in the pathogenesis of many autoimmune diseases...
November 27, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/29207601/dissecting-the-mechanisms-involved-in-anti-human-t-lymphocyte-immunoglobulin-atg-induced-tolerance-in-the-setting-of-allogeneic-stem-cell-transplantation-potential-implications-for-graft-versus-host-disease
#10
Katia Beider, David Naor, Valeria Voevoda, Olga Ostrovsky, Hanna Bitner, Evgenia Rosenberg, Nira Varda-Bloom, Victoria Marcu-Malina, Jonathan Canaani, Ivetta Danilesko, Avichai Shimoni, Arnon Nagler
Polyclonal anti-human thymocyte globulins (ATG) have been recently shown to significantly reduce the incidence of graft versus host disease (GVHD) post allogeneic stem cell transplantation (HSCT) from both sibling and unrelated donors. Induction of regulatory T cells has been suggested as one of the possible mechanisms. The aim of current study was to further characterize the T cell populations induced by ATG treatment and to delineate the mechanisms involved in ATG-induced tolerance. Phenotypic characterization revealed a significant increase in the expression of FoxP3, GITR, CD95, PD-1 and ICOS as well as the complement inhibitory molecules CD55, CD58 and CD59 on CD4+CD25+ T cells upon ATG treatment...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29197677/distinct-biomarker-profiles-in-ex-vivo-t-cell-depletion-graft-manipulation-strategies-cd34-selection-vs-cd3-19-depletion-in-matched-sibling-allogeneic-peripheral-blood-stem-cell-transplantation
#11
Caroline R Cantilena, Sawa Ito, Xin Tian, Prachi Jain, Fariba Chinian, Prathima Anandi, Keyvan Keyvanfar, Debbie Draper, Eleftheria Koklanaris, Sara Hauffe, Jeanine Superata, David Stroncek, Pawel Muranski, A John Barrett, Minoo Battiwalla
Various approaches have been developed for ex vivo T cell depletion in allogeneic stem cell transplantation to prevent graft versus host disease (GVHD). However, direct comparisons between T-cell depletion strategies have not been well studied. We evaluated cellular and plasma biomarkers in two different graft manipulation strategies: CD3+CD19+ cell depletion (CD3/19D) versus CD34+ selection (CD34S) and their association with clinical outcomes. Identical conditions including the myeloablative preparative regimen, HLA-identical sibling donor, GVHD prophylaxis, and graft source were used for each cohort...
November 29, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29193502/foxp3-mutations-causing-early-onset-insulin-requiring-diabetes-but-without-other-features-of-immune-dysregulation-polyendocrinopathy-enteropathy-x-linked-syndrome
#12
Jessica L Hwang, Soo-Young Park, Honggang Ye, May Sanyoura, Ashley N Pastore, David Carmody, Daniela Del Gaudio, Janna F Wilson, Craig L Hanis, Xiaoming Liu, Gil Atzmon, Benjamin Glaser, Louis H Philipson, Siri Atma W Greeley
Diabetes occurs in 1/90 000 to 1/160 000 births and when diagnosed under 6 months of age is very likely to have a primary genetic cause. FOXP3 encodes a transcription factor critical for T regulatory cell function and mutations are known to cause "immune dysregulation, polyendocrinopathy (including insulin-requiring diabetes), enteropathy, X-linked" (IPEX) syndrome. This condition is often fatal unless patients receive a bone-marrow transplant. Here we describe the phenotype of male neonates and infants who had insulin-requiring diabetes without other features of IPEX syndrome and were found to have mutations in FOXP3...
November 29, 2017: Pediatric Diabetes
https://www.readbyqxmd.com/read/29176976/engineering-specificity-and-function-of-therapeutic-regulatory-t-cells
#13
REVIEW
Jenny L McGovern, Graham P Wright, Hans J Stauss
Adoptive therapy with polyclonal regulatory T cells (Tregs) has shown efficacy in suppressing detrimental immune responses in experimental models of autoimmunity and transplantation. The lack of specificity is a potential limitation of Treg therapy, as studies in mice have demonstrated that specificity can enhance the therapeutic potency of Treg. We will discuss that vectors encoding T cell receptors or chimeric antigen receptors provide an efficient gene-transfer platform to reliably produce Tregs of defined antigen specificity, thus overcoming the considerable difficulties of isolating low-frequency, antigen-specific cells that may be present in the natural Treg repertoire...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29175009/treatment-with-mtor-inhibitors-after-liver-transplantation-enables-a-sustained-increase-in-regulatory-t-cells-while-preserving-their-suppressive-capacity
#14
Khaldoun Ghazal, Fabien Stenard, Géraldine Dahlqvist, Clément Barjon, Lynda Aoudjehane, Olivier Scatton, Filomena Conti
BACKGROUND: The mammalian targets of rapamycin (mTOR) inhibitors (sirolimus [SRL] and everolimus [EVR]) are used after transplantation for their immunosuppressive activity. Regulatory T-cells (Tregs) play a crucial role in immune tolerance. mTOR inhibitors appear to preserve Tregs, unlike Tacrolimus (Tac). AIM: The aim of this study was to evaluate the number and function of Tregs in liver transplant recipients before and after conversion from Tac to mTOR inhibitors...
November 22, 2017: Clinics and Research in Hepatology and Gastroenterology
https://www.readbyqxmd.com/read/29167674/a-new-immunosuppressive-molecule-emodin-induces-both-cd4-foxp3-and-cd8-cd122-regulatory-t-cells-and-suppresses-murine-allograft-rejection
#15
Feifei Qiu, Huazhen Liu, Chun-Ling Liang, Golay D Nie, Zhenhua Dai
Due to vigorous alloimmunity, an allograft is usually rejected without any conventional immunosuppressive treatment. However, continuous global immunosuppression may cause severe side effects, including tumors and infections. Mounting evidence has shown that cyclosporine (CsA), a common immunosuppressant used in clinic, impedes allograft tolerance by dampening regulatory T cells (Tregs), although it inhibits allograft rejection at the same time. Therefore, it is necessary to seek an alternative immunosuppressive drug that spares Tregs with high efficiency in suppression but low toxicity...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29167234/route-of-antigen-presentation-can-determine-the-selection-of-foxp3-dependent-or-foxp3-independent-dominant-immune-tolerance
#16
Ana Agua-Doce, Marta Caridade, Vanessa G Oliveira, Lisa Bergman, Maria C Lafaille, Juan J Lafaille, Jocelyne Demengeot, Luis Graca
It has been shown that dominant tolerance, namely in transplantation, requires Foxp3(+) regulatory T cells. Although most tolerance-inducing regimens rely on regulatory T cells, we found that induction of tolerance to proteins in aluminum hydroxide can be achieved in Foxp3-deficient mice using nondepleting anti-CD4 Abs. This type of tolerance is Ag specific, and tolerant mice retain immune competence to respond to unrelated Ags. We demonstrated with chicken OVA-specific TCR-transgenic mice that the same tolerizing protocol (CD4 blockade) and the same target Ag (OVA) achieves Foxp3-dependent transplantation tolerance to OVA-expressing skin grafts, but Foxp3-independent tolerance when the Ag is provided as OVA-aluminum hydroxide...
November 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29163527/engineered-tolerance-tailoring-development-function-and-antigen-specificity-of-regulatory-t-cells
#17
REVIEW
Nicholas A J Dawson, Jens Vent-Schmidt, Megan K Levings
Regulatory T cells (Tregs) are potent suppressors of immune responses and are currently being clinically tested for their potential to stop or control undesired immune responses in autoimmunity, hematopoietic stem cell transplantation, and solid organ transplantation. Current clinical approaches aim to boost Tregs in vivo either by using Treg-promoting small molecules/proteins and/or by adoptive transfer of expanded Tregs. However, the applicability of Treg-based immunotherapies continues to be hindered by technical limitations related to cell isolation and expansion of a pure, well-characterized, and targeted Treg product...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29157299/the-similarities-between-smdcs-and-regdcs-in-alleviating-the-immune-injury-caused-by-transplantation-of-hepatocytes-differentiated-from-escs
#18
Cheng Zhang, Wenwei Liao, Bing Cai, Furong Liu, Qiong Ke, Xiaofeng Zhu, Xiaoshun He, Anbin Hu
BACKGROUND: This study aimed to investigate the tolerogenic mechanisms induced by semimature dendritic cells (smDCs) and regulatory dendritic cells (regDCs) after transplantation of hepatocytes differentiated from mouse embryonic stem cells (ESCs) and to confirm the low immunogenicity of hepatocytes differentiated from ESCs. METHODS: Green fluorescent protein-labeled ESCs collected from 129 mice were cultured to differentiate into hepatocytes. smDCs and regDCs were cultured in vitro...
November 21, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29150659/ectopic-foxp3-expression-preserves-primitive-features-of-human-hematopoietic-stem-cells-while-impairing-functional-t-cell-differentiation
#19
F R Santoni de Sio, L Passerini, M M Valente, F Russo, L Naldini, M G Roncarolo, R Bacchetta
FOXP3 is the transcription factor ruling regulatory T cell function and maintenance of peripheral immune tolerance, and mutations in its coding gene causes IPEX autoimmune syndrome. FOXP3 is also a cell-cycle inhibitor and onco-suppressor in different cell types. In this work, we investigate the effect of ectopic FOXP3 expression on HSC differentiation and we challenged this approach as a possible HSC-based gene therapy for IPEX. FOXP3-expressing HSC showed reduced proliferation ability and increased maintenance of primitive markers in vitro in both liquid and OP9-ΔL1 co-cultures...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29143918/induction-of-cd4-cd25-foxp3-regulatory-t-cells-by-mesenchymal-stem-cells-is-associated-with-runx-complex-factors
#20
Maryam Khosravi, Ali Bidmeshkipour, Ali Moravej, Suzzan Hojjat-Assari, Sina Naserian, Mohammad Hossein Karimi
Among the particular immunomodulation properties of mesenchymal stem cells (MSCs), one relies on their capacity to regulatory T cell (Treg) induction from effector T cells. Stable expression of Foxp3 has a dominant role in suppressive phenotype and stability of induced regulatory T cells (iTregs). How MSCs induce stable Foxp3 expression in iTregs remains unknown. We previously showed MSCs could enhance demethylation of Treg-specific demethylated region (TSDR) in iTregs in cell-cell contact manner (unpublished data)...
November 16, 2017: Immunologic Research
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