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https://www.readbyqxmd.com/read/28930796/navigating-t-cell-immunometabolism-in-transplantation
#1
Naoki Tanimine, Laurence A Turka, Bhavana Priyadharshini
Recently, a new discipline termed "immunometabolism" has transformed the field of immunology. It encompasses the study of the intrinsic metabolic pathways of different immune subsets and their impact on cellular fate and function. For instance, broadly speaking, pro-inflammatory cells depend upon glycolysis and glutamine oxidation while cells involved in anti-inflammatory response such as Foxp3+ regulatory T cells (Tregs) utilize predominantly fatty acid oxidation. However, while a useful paradigm, this actually is a reductionist view and the engagement of these metabolic pathways is not mutually exclusive between these subsets...
September 19, 2017: Transplantation
https://www.readbyqxmd.com/read/28926189/environmental-peer-pressure-cd4-t-cell-help-in-tolerance-and-transplantation
#2
REVIEW
Dana Tedesco, Arash Grakoui
The liver participates in a multitude of metabolic functions that are critical for sustaining human life. Despite constant encounters with antigenic-rich intestinal blood, oxidative stress and metabolic intermediates, there is no appreciable immune response. Interestingly, patients undergoing orthotopic liver transplantation benefit from a high rate of graft acceptance in comparison to other solid organ transplant recipients. In fact, co-transplantation of a donor liver in tandem with a rejection-prone graft increases the likelihood of graft acceptance...
September 19, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28923634/variation-of-cd4-cd25-foxp3-regulatory-t-cells-and-th17-cells-in-the-peripheral-blood-of-human-liver-allograft-patients-with-long-term-survival
#3
G Shi, Q Zeng, Z Zhao, W Li, J Dou
BACKGROUND: Monitoring of peripheral blood (PB) lymphocyte subpopulation counts may be useful to underlie immune status after liver transplantation (LT). We aimed at exploring the variation of regulatory cells and Th17 in the PB of liver allograft patients with long-term survival. METHODS: Forty-two patients who took FK506 drugs were divided into 3 groups: patients who survived for 6 months to 3 years were in the Tac1 group (n = 15), those who survived for 3-10 years were in the Tac2 group (n = 15), and those who survived for >10 years were in the Tac3 group (n = 12)...
October 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28901194/acute-renal-graft-versus-host-disease-in-a-murine-model-of-allogeneic-bone-marrow-transplantation
#4
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 is associated with a poor prognosis. Generally, the kidneys are assumed to not be no direct targets 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 major histocompatibility complex (MHC)-mismatched model of BALB/c mice conditioned and transplanted according to 2 different intensity protocols...
August 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28901186/recipient-adipose-derived-stem-cells-enhance-recipient-cell-engraftment-and-prolong-allotransplant-survival-in-a-miniature-swine-hind-limb-model
#5
Yur-Ren Kuo, Chien-Chang Chen, Yen-Chou Chen, Ching-Ming Chien
Donor mesenchymal stem cells (MSCs) could prolong vascularized composite allotransplantation (VCA) survival in our previous studies. However, recipient adipose tissue is easier to harvest than donor tissue for preconditioning modulation. Hence, this study investigated the efficacy of recipient autologous adipose-derived stem cells (rADSCs) for VCA survival. The heterotopic hind-limb transplantation from female donor to male recipient was performed in outbred miniature swine. Group I ( n = 6) was untreated controls...
August 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28900605/histopathological-analysis-of-infiltrating-t-cell-subsets-in-acute-t-cell-mediated-rejection-in-the-kidney-transplant
#6
Francisco Salcido-Ochoa, Susan Swee-Shan Hue, Siyu Peng, Zhaoxiang Fan, Reiko Lixiang Li, Jabed Iqbal, John Carson Allen, Alwin Hwai Liang Loh
AIM: To compare the differential immune T cell subset composition in patients with acute T cell-mediated rejection in the kidney transplant with subset composition in the absence of rejection, and to explore the association of their respective immune profiles with kidney transplant outcomes. METHODS: A pilot cross-sectional histopathological analysis of the immune infiltrate was performed using immunohistochemistry in a cohort of 14 patients with acute T cell-mediated rejection in the kidney transplant and 7 kidney transplant patients with no rejection subjected to biopsy to investigate acute kidney transplant dysfunction...
August 24, 2017: World Journal of Transplantation
https://www.readbyqxmd.com/read/28893978/gut-bacteria-from-multiple-sclerosis-patients-modulate-human-t-cells-and-exacerbate-symptoms-in-mouse-models
#7
Egle Cekanaviciute, Bryan B Yoo, Tessel F Runia, Justine W Debelius, Sneha Singh, Charlotte A Nelson, Rachel Kanner, Yadira Bencosme, Yun Kyung Lee, Stephen L Hauser, Elizabeth Crabtree-Hartman, Ilana Katz Sand, Mar Gacias, Yungjiao Zhu, Patrizia Casaccia, Bruce A C Cree, Rob Knight, Sarkis K Mazmanian, Sergio E Baranzini
The gut microbiota regulates T cell functions throughout the body. We hypothesized that intestinal bacteria impact the pathogenesis of multiple sclerosis (MS), an autoimmune disorder of the CNS and thus analyzed the microbiomes of 71 MS patients not undergoing treatment and 71 healthy controls. Although no major shifts in microbial community structure were found, we identified specific bacterial taxa that were significantly associated with MS. Akkermansia muciniphila and Acinetobacter calcoaceticus, both increased in MS patients, induced proinflammatory responses in human peripheral blood mononuclear cells and in monocolonized mice...
September 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28880742/decreased-levels-of-th17-cells-are-associated-with-invasion-fungal-infections-after-allogeneic-hematopoietic-stem-cell-transplantation
#8
Ling Wang, Peng Zhao, Chunlei Shi, Ying Li, Ketao Lan, Mingzhe Han
BACKGROUND: Delayed immune reconstitution is an important risk factor for increased susceptibility to fungal pathogens. However, little is known about the association between the recovery of CD4(+)T cell subsets and invasion fungal infections (IFIs) in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The aim of the study was to analyze the immune reconstitution characteristics of CD4(+)T cell subsets and their association with the incidence of IFIs over the first 3 months after allo-HSCT...
September 7, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/28872082/-relationship-between-the-methylation-status-of-stat3-promoter-dna-in-peripheral-blood-cd4-t-cells-from-patients-after-allo-hsct-and-agvhd
#9
Yajing Xu, Yuanyuan Zhang, Yan Chen, Bin Fu, Jing Yang, Fangping Chen
To study the relationship between acute graft versus host disease (aGVHD) and the methylation status of the STAT3 promoter in peripheral blood CD4+ T cells from patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT).
 Methods: We collected 40 patients who underwent allo-HSCT from HLA-identical sibling donors. Serum IL-10, TGF-β1, IL-17A and IL-17F levels were detected by ELISA. Foxp3 cytotoxic T-lymphocyte-associated protein 4 (CTLA4), IL-10, TGF-β1, RORγt, IL-17A and IL-17F mRNA levels in CD4+ T cells were measured by real-time PCR...
August 28, 2017: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/28869950/interleukin-10-gene-modified-dendritic-cell-induced-type-1-regulatory-t-cells-induce-transplant-tolerance-and-impede-graft-versus-host-disease-after-allogeneic-stem-cell-transplantation
#10
Jiangbo Wan, Fang Huang, Siguo Hao, Weiwei Hu, Chuanxu Liu, Wenhao Zhang, Xiaohui Deng, Linjun Chen, Liyuan Ma, Rong Tao
BACKGROUND/AIMS: Tr1 cells can induce peripheral tolerance to self- and foreign antigens, and have been developed as a therapeutic tool for the induction of tolerance to transplanted tissue. We explored the feasibility of generating Tr1 cells by using IL-10 gene-modified recipient DCs (DCLV-IL-10) to stimulate donor naive CD4+ T cells. We also investigated some biological properties of Tr1 cells. METHODS: DCLV-IL-10 were generated through DCs transduced with a lentivirus vector carrying the IL-10 gene, and Tr1 cells were produced by using DCLV-IL-10 to stimulate naive CD4+ T cells...
August 31, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28842469/a20-restrains-thymic-regulatory-t-cell-development
#11
Julius Clemens Fischer, Vera Otten, Maike Kober, Christoph Drees, Marc Rosenbaum, Martina Schmickl, Simon Heidegger, Rudi Beyaert, Geert van Loo, Xian Chang Li, Christian Peschel, Marc Schmidt-Supprian, Tobias Haas, Silvia Spoerl, Hendrik Poeck
Maintaining immune tolerance requires the production of Foxp3-expressing regulatory T (Treg) cells in the thymus. Activation of NF-κB transcription factors is critically required for Treg cell development, partly via initiating Foxp3 expression. NF-κB activation is controlled by a negative feedback regulation through the ubiquitin editing enzyme A20, which reduces proinflammatory signaling in myeloid cells and B cells. In naive CD4(+) T cells, A20 prevents kinase RIPK3-dependent necroptosis. Using mice deficient for A20 in T lineage cells, we show that thymic and peripheral Treg cell compartments are quantitatively enlarged because of a cell-intrinsic developmental advantage of A20-deficient thymic Treg differentiation...
August 25, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28827518/activated-protein-c-protects-from-gvhd-via-par2-par3-signalling-in-regulatory-t-cells
#12
Satish Ranjan, Alexander Goihl, Shrey Kohli, Ihsan Gadi, Mandy Pierau, Khurrum Shahzad, Dheerendra Gupta, Fabian Bock, Hongjie Wang, Haroon Shaikh, Thilo Kähne, Dirk Reinhold, Ute Bank, Ana C Zenclussen, Jana Niemz, Tina M Schnöder, Monika Brunner-Weinzierl, Thomas Fischer, Thomas Kalinski, Burkhart Schraven, Thomas Luft, Jochen Huehn, Michael Naumann, Florian H Heidel, Berend Isermann
Graft-vs.-host disease (GvHD) is a major complication of allogenic hematopoietic stem-cell(HSC) transplantation. GvHD is associated with loss of endothelial thrombomodulin, but the relevance of this for the adaptive immune response to transplanted HSCs remains unknown. Here we show that the protease-activated protein C (aPC), which is generated by thrombomodulin, ameliorates GvHD aPC restricts allogenic T-cell activation via the protease activated receptor (PAR)2/PAR3 heterodimer on regulatory T-cells (Tregs, CD4(+)FOXP3(+))...
August 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28819166/histone-protein-deacetylase-11-targeting-promotes-foxp3-treg-function
#13
Jianbing Huang, Liqing Wang, Satinder Dahiya, Ulf H Beier, Rongxiang Han, Arabinda Samanta, Joel Bergman, Eduardo M Sotomayor, Edward Seto, Alan P Kozikowski, Wayne W Hancock
Current interest in Foxp3+ T-regulatory (Treg) cells as therapeutic targets in transplantation is largely focused on their harvesting pre-transplant, expansion and infusion post-transplantation. An alternate strategy of pharmacologic modulation of Treg function using histone/protein deacetylase inhibitors (HDACi) may allow more titratable and longer-term dosing. However, the effects of broadly acting HDACi vary, such that HDAC isoform-selective targeting is likely required. We report data from mice with constitutive or conditional deletion of HDAC11 within Foxp3+ Treg cells, and their use, along with small molecule HDAC11 inhibitors, in allograft models...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28808483/therapeutic-immune-monitoring-of-cd4-cd25-t-cells-in-chronic-myeloid-leukemia-patients-treated-with-tyrosine-kinase-inhibitors
#14
Ziyuan Lu, Na Xu, Xuan Zhou, Guanlun Gao, Lin Li, Jixian Huang, Yuling Li, Qisi Lu, Bolin He, Chengyun Pan, Xiaoli Liu
Tyrosine kinase inhibitors (TKIs), including imatinib, dasatinib and nilotinib, are effective forms of therapy for various types of solid cancers and Philadelphia chromosome-positive (Ph(+)) chronic myeloid leukemia. A number of TKIs have been known to have strong effects on T cells, particularly cluster of differentiation (CD) 4(+)CD25(+) T cells, also known as regulatory T cells (Tregs). There is currently a deficit in the available clinical data regarding this area of study. In the present study, a total of 108 peripheral blood samples were collected from patients with chronic myeloid leukemia (CML) at diagnosis (n=31), and at 3 and 6 months following treatment with TKI [imatinib (n=12), dasatinib (n=11) and nilotinib groups (n=8)] and healthy controls (n=15)...
August 2017: Oncology Letters
https://www.readbyqxmd.com/read/28802588/t-cell-costimulation-blockade-promotes-transplantation-tolerance-in-combination-with-sirolimus-and-post-transplantation-cyclophosphamide-for-haploidentical-transplantation-in-children-with-severe-aplastic-anemia
#15
Sarita Rani Jaiswal, Prakash Bhakuni, Shamsuz Zaman, Satish Bansal, Priyanka Bharadwaj, Sneh Bhargava, Suparno Chakrabarti
We conducted a pilot study employing extended T cell costimulation blockade (COSBL) with Abatacept along with sirolimus and post-transplantation cyclophosphamide (PTCy) in 10 patients (median age 12) with severe aplastic anemia (SAA). Nine patients engrafted in the COSBL group, compared to all 10 patients (median 14 vs 13days) treated on PTCy protocols without abatacept (CONTROL group). The incidence of acute graft-versus-host disease (GVHD) was 10.5% in the COSBL group compared to 50% in the CONTROL group (p=0...
August 9, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28802587/pre-transplant-infusion-of-donor-derived-dendritic-cells-maintained-at-the-immature-stage-by-sinomenine-increases-splenic-foxp3-tregs-in-recipient-rats-after-renal-allotransplantation
#16
Lian Li, Zhigang Luo, Zhe Song, Liwen Zheng, Tuo Chen
OBJECTIVE: The immunosuppressive mechanism of sinomenine in organ allotransplantation was investigated, especially its effect of blocking dendritic cell (DC) maturation, which might influence the frequency of regulatory T cells (Tregs). METHODS: Bone marrow cells from male donor Wistar rats were induced to differentiate into DCs in vitro in the presence or absence of sinomenine, and characterized by flow cytometry. These two groups of DCs were respectively injected into male recipient Sprague-Dawley rats via the tail vein, at both high and low doses...
August 9, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28777210/rapamycin-prolongs-graft-survival-and-induces-cd4-ifn-%C3%AE-il-10-regulatory-type-1-cells-in-old-recipient-mice
#17
Markus Quante, Timm Heinbokel, Karoline Edtinger, Koichiro Minami, Hirofumi Uehara, Yeqi Nian, Haruhito Azuma, Reza Abdi, Abdallah Elkhal, Stefan G Tullius
BACKGROUND: Although the elderly represents a rapidly growing population among transplant recipients, age-specific aspects have not been considered sufficiently in clinical trials. Moreover, age-specific effects of immunosuppressive therapies remain poorly understood. METHODS: Here, we assessed the impact of Rapamycin on alloimmune responses in old recipients using a fully MHC-mismatched murine transplantation model. RESULTS: Old untreated recipients displayed a prolonged skin graft survival compared to their young counterparts, an observation that confirmed data of our previous experiments...
August 2, 2017: Transplantation
https://www.readbyqxmd.com/read/28769930/anti-interleukin-6-promotes-allogeneic-bone-marrow-engraftment-and-prolonged-graft-survival-in-an-irradiation-free-murine-transplant-model
#18
Nicolas Granofszky, Andreas M Farkas, Moritz Muckenhuber, Benedikt Mahr, Lukas Unger, Svenja Maschke, Nina Pilat, Raimund Holly, Mario Wiletel, Heinz Regele, Thomas Wekerle
Transfer of recipient regulatory T cells (Tregs) induces mixed chimerism and tolerance in an irradiation-free bone marrow (BM) transplantation (BMT) model involving short-course co-stimulation blockade and mTOR inhibition. Boosting endogenous Tregs pharmacologically in vivo would be an attractive alternative avoiding the current limitations of performing adoptive cell therapy in the routine clinical setting. Interleukin-6 (IL-6) potently inhibits Treg differentiation and its blockade was shown to increase Treg numbers in vivo...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28757397/low-utility-of-serum-25-hydroxyvitamin-d3-and-1-25-dihydroxyvitamin-d3-in-predicting-peripheral-treg-and-th17-cell-counts-in-esrd-and-renal-transplant-patients
#19
Mostafa G Aly, Li Zhu, Rolf Weimer, Gerhard Opelz, Christian Morath, Ruben Kuon, Mohammed Tohamy, Gamal Saadi, Mona Soliman, Walaa Ibrahim, Volker Daniel
BACKGROUND: Vitamin D has shown an immune-modulatory effect in different studies. Vitamin D stimulates Tregs and inhibits Th17 cells. The immune-modulatory role of vitamin D in chronic kidney disease (CKD) and renal transplant patients is unclear. We measured whether different serum levels of vitamin D were associated with an increased or decreased presence of lymphocyte subsets including Treg and Th17 cells in end-stage renal disease (ESRD) and renal transplant recipients. METHODS: Eighty-seven renal transplant recipients and 53 end-stage renal disease (ESRD) patients were enrolled in this study...
July 27, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28746369/single-and-combined-effect-of-retinoic-acid-and-rapamycin-modulate-the-generation-activity-and-homing-potential-of-induced-human-regulatory-t-cells
#20
Enzo Candia, Paz Reyes, Camila Covian, Francisco Rodriguez, Nicolas Wainstein, Jorge Morales, Claudio Mosso, Mario Rosemblatt, Juan Alberto Fierro
Adoptive transfer of CD4+CD25+FOXP3+ regulatory T cells (Treg cells) has been successfully utilized to treat graft versus host disease and represents a promising strategy for the treatment of autoimmune diseases and transplant rejection. The aim of this study was to evaluate the effects of all-trans retinoic acid (atRA) and rapamycin (RAPA) on the number, phenotype, homing markers expression, DNA methylation, and function of induced human Treg cells in short-term cultures. Naive T cells were polyclonally stimulated and cultured for five days in the presence of different combinations of IL-2, TGF-β1, atRA and RAPA...
2017: PloS One
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