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Regulatory B cell in transplantation

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https://www.readbyqxmd.com/read/28109145/-short-term-use-of-rapamycin-combined-with-tregs-prolongs-mouse-cardiac-graft-survival-but-attenuates-recipient-s-anti-tumor-immunity
#1
Ting Yan, Chen Luo, Xianmo Yang, Lei Ji, Shiqiao Luo
Objective To study the effect of short-term use of rapamycin(Rap) combined with regulatory T cells (Tregs) on the long-time survival of allogeneic mouse cardiac transplant, and its impact on the anti-tumor immunity of recipient. MethodsMouse Tregs were purified from recipients' spleen by magnetic activated cell sorting (MACS), and expanded by CD3/CD28 monoclonal antibody immunomagnetic beads and 2000 U/mL recombinant mouse IL-2 (rmIL-2) ex vivo. The purity was tested by fluorescence-activated cell sorting (FACS)...
February 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28103645/prognostic-impact-of-lymphocyte-subpopulations-in-peripheral-blood-after-hematopoietic-stem-cell-transplantation-for-hematologic-malignancies
#2
Sang Hyuk Park, Chan-Jeoung Park, Borae G Park, Mi-Hyun Bae, Bo-Hyun Kim, Young-Uk Cho, Seongsoo Jang, Ae Ja Park, Dae-Young Kim, Jung-Hee Lee, Je-Hwan Lee, Kyoo-Hyung Lee
BACKGROUND: We prospectively evaluated prognostic value of lymphocyte subpopulations in peripheral blood of allogeneic hematopoietic stem cell transplant (HSCT)-recipients. METHODS: 113 allogeneic HSCT (47 sibling matched, 37 unrelated matched, 29 haploidentical)-performed patients diagnosed as AML (n=66), ALL (n=28) and MDS (n=19) were prospectively enrolled. 14 lymphocyte subpopulations were quantified by flow cytometry of PB at specific time-points after HSCT, and their prognostic impacts were analyzed...
January 19, 2017: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/28100001/transplantation-tolerance-don-t-forget-about-the-b-cells
#3
REVIEW
Anita S Chong, Stella H Khiew
Establishing a state of transplantation tolerance that leads to indefinite graft survival without the need for lifelong immunosuppression has been successfully achieved in limited numbers of transplant recipients in the clinic. These successes led to studies aimed at identifying potential biomarkers that diagnose allograft tolerance and identify the patients most amenable to drug minimization, and implicated an enriched B cell signature of tolerance. The emergence of a specialized subset of regulatory B cell (Bregs) that possess immune-modulatory function in inflammation and autoimmune disease, raised the possibility that Bregs play critical roles in the promotion of transplantation tolerance and that Bregs are the underlying explanation for the B cell signature of tolerance...
January 18, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28097811/fc-silent-anti-cd154-domain-antibody-effectively-prevents-non-human-primate-renal-allograft-rejection
#4
Steven C Kim, Walter Wakwe, Laura B Higginbotham, David V Mathews, Cynthia P Breeden, Allison C Stephenson, Joe Jenkins, Elizabeth Strobert, Karen Price, Laura Price, Robert Kuhn, Haiqing Wang, Aaron Yamniuk, Suzanne Suchard, Alton B Farris, Thomas C Pearson, Christian P Larsen, Mandy L Ford, Anish Suri, Steven Nadler, Andrew B Adams
The advent of costimulation blockade provides the prospect for targeted therapy with improved graft survival in transplant patients. Perhaps the most effective costimulation blockade in experimental models is the use of reagents to block the CD40/CD154 pathway. Unfortunately, successful clinical translation of anti-CD154 therapy has not been achieved. In an attempt to develop an agent that is as effective as previous CD154 blocking antibodies but lacks the risk of thromboembolism, we evaluated the efficacy and safety of a novel anti-human CD154 domain antibody (dAb, BMS-986004)...
January 17, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28097735/autoimmune-enteropathy-and-hepatitis-in-pediatric-heart-transplant-recipient
#5
Kimberly Lewis, Ryan Butts, J Antonio Quiros, Michelle Hudspeth, Katherine Twombley, Andrew Savage, Sally Self, Ali Burnette, Shaoli Sun
AIE is a rare disorder in children that presents with severe diarrhea and malabsorption, caused by immune-mediated damage to intestinal mucosa. AIE is often associated with various syndromes of immunodeficiency including IPEX syndrome (immune dysregulation, polyendocrinopathy and enteropathy, X-linked). Dysfunctional T regulatory cells are the source of pathology in both IPEX syndrome and AIE as they are essential in maintaining tolerance to self-antigens and eliminating autoreactive B cells. This case report describes a 10-year-old cardiac transplant and total thymectomy patient on chronic immunosuppression with tacrolimus that presented with AIE and extraintestinal manifestations of cyclical hepatitis...
January 17, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28095351/level-of-granzyme-b-positive-t-regulatory-cells-is-a-strong-predictor-biomarker-of-acute-graft-versus-host-disease-after-day-30-after-allo-hsct
#6
Mikhail Y Drokov, Julia O Davydova, Larisa A Kuzmina, Irina V Galtseva, Nikolay M Kapranov, Vera A Vasilyeva, Darya S Dubnyak, Olga M Koroleva, Ekaterina D Mikhalcova, Natalia N Popova, Elena N Parovichnikova, Valery G Savchenko
Acute Graft-versus-host-disease (aGVHD), the major complication and one of the main causes of poor outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Nowadays there are no widely accepted cell, plasma or another biomarker that can be used for aGVHD prediction. We hypothesized that a level of Granzyme B-positive T regulatory (GZMB-positive Treg) cells on day+30 after allo-HSCT could be the measure of immune response suppression and could predict aGVHD development after day +30. We applied a widespread and easy-to-perform method of multicolor flow cytometry to measure level of GZMB-positive Treg cells...
January 10, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28058210/biology-of-chronic-graft-vs-host-disease-immune-mechanisms-and-progress-in-biomarker-discovery
#7
REVIEW
Richard B Presland
Chronic graft-vs-host disease (cGVHD) is the leading cause of long-term morbidity and mortality following allogeneic hematopoietic stem cell transplantation. It presents as a chronic inflammatory and sclerotic autoimmune-like condition that most frequently affects the skin, oral mucosa, liver, eyes and gastrointestinal tract. Both clinical and animal studies have shown that multiple T cell subsets including Th1, Th2, Th17, T follicular helper cells and regulatory T-cells play some role in cGVHD development and progression; B cells also play an important role in the disease including the production of antibodies to HY and nuclear antigens that can cause serious tissue damage...
December 24, 2016: World Journal of Transplantation
https://www.readbyqxmd.com/read/28042143/mesenchymal-stem-cells-ameliorate-b-cell-mediated-immune-responses-and-increase-il-10-expressing-regulatory-b-cells-in-an-ebi3-dependent-manner
#8
Kyung-Ah Cho, Jun-Kyu Lee, Yu-Hee Kim, Minhwa Park, So-Youn Woo, Kyung-Ha Ryu
Effector B cells are central contributors to the development of autoimmune disease by activating autoreactive T cells, producing pro-inflammatory cytokines and organizing ectopic lymphoid tissue. Conversely, IL-10-producing regulatory B (Breg) cells have pivotal roles in maintaining immunological tolerance and restraining excessive inflammation in autoinflammatory disease. Thus, regulating the equilibrium between antibody-producing effector B cells and Breg cells is critical for the treatment of autoimmune disease...
January 2, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28029430/reduced-human-transitional-b-cell-t1-t2-ratio-is%C3%A2-associated-with-subsequent-deterioration-in%C3%A2-renal-allograft-function
#9
Aravind Cherukuri, Alan D Salama, Clive R Carter, Douglas Landsittel, Gururaj Arumugakani, Brendan Clark, David M Rothstein, Richard J Baker
Human transitional B cells express relatively high IL-10 and low TNF-α levels, which correlate with B regulatory activity in vitro. Herein, we aim to further define B regulatory phenotype and determine whether B regulatory activity can serve as a prognostic marker for renal allograft dysfunction (graft loss or 2-fold fall in estimated glomerular filtration rate). Transitional B cells can be divided into T1 and T2 subsets based on surface phenotype. T1 cells express a significantly higher ratio of IL-10 to TNF-α than T2 cells or other B subsets...
October 28, 2016: Kidney International
https://www.readbyqxmd.com/read/28019030/histone-deacetylase-inhibitors-suppress-abo-transcription-in-vitro-leading-to-reduced-expression-of-the-antigens
#10
Yoichiro Takahashi, Rieko Kubo, Rie Sano, Tamiko Nakajima, Keiko Takahashi, Momoko Kobayashi, Hiroshi Handa, Junichi Tsukada, Yoshihiko Kominato
BACKGROUND: The ABO system is of fundamental importance in the fields of transfusion and transplantation and has apparent associations with certain diseases, including cardiovascular disorders. ABO expression is reduced in the late phase of erythroid differentiation in vitro, whereas histone deacetylase inhibitors (HDACIs) are known to promote cell differentiation. Therefore, whether or not HDACIs could reduce the amount of ABO transcripts and A or B antigens is an intriguing issue. STUDY DESIGN AND METHODS: Quantitative polymerase chain reactions were carried out for the ABO transcripts in erythroid-lineage K562 and epithelial-lineage KATOIII cells after incubation with HDACIs, such as sodium butyrate, panobinostat, vorinostat, and sodium valproate...
December 26, 2016: Transfusion
https://www.readbyqxmd.com/read/28017877/negative-regulation-of-hla-dr-expression-on-endothelial-cells-by-anti-blood-group-a-b-antibody-ligation-and-mtor-inhibition
#11
Kenta Iwasaki, Yuko Miwa, Kazuharu Uchida, Yasuhiro Kodera, Takaaki Kobayashi
Donor-specific antibody (DSA), particularly against HLA class II, is a major cause of chronic antibody-mediated rejection (CAMR) after transplantation, although ABO-incompatible kidney transplantation has recently demonstrated favorable graft outcomes. The condition of no injury even in the presence of anti-donor antibody has been referred to as "accommodation", which would be one of the key factors for successful long-term graft survival. The purpose of this study was to analyze the beneficial effect of anti-blood group A/B antibody ligation on endothelial cells against HLA-DR antibody-mediated, complement-dependent cytotoxicity (CDC)...
December 23, 2016: Transplant Immunology
https://www.readbyqxmd.com/read/28009481/renal-allograft-survival-in-nonhuman-primates-infused-with-donor-antigen-pulsed-autologous-regulatory-dendritic-cells
#12
M B Ezzelarab, D Raich-Regue, L Lu, A F Zahorchak, A Perez-Gutierrez, A Humar, M Wijkstrom, M Minervini, R W Wiseman, D K C Cooper, A E Morelli, A W Thomson
Systemic administration of autologous regulatory dendritic cells (DCreg; unpulsed or pulsed with donor antigen [Ag]), prolongs allograft survival and promotes transplant tolerance in rodents. Here, we demonstrate that nonhuman primate (NHP) monocyte-derived DCreg pre-loaded with cell membrane vesicles from allogeneic PBMC, induce T cell hyporesponsiveness to donor alloAg in vitro. These donor alloAg-pulsed autologous DCreg (1.4-3.6 x 10(6) /kg) were administered intravenously, one day before MHC-mismatched renal transplantation to rhesus monkeys treated with costimulation blockade (cytotoxic T lymphocyte Ag 4 [CTLA4] Ig) and tapered rapamycin...
December 23, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/28006867/differential-profile-of-activated-regulatory-t-cell-subsets-and-micrornas-in-tolerant-liver-transplant-recipients
#13
B Revilla-Nuin, A de Bejar, L Martínez-Alarcón, J I Herrero, C M Martínez-Cáceres, P Ramírez, A Baroja-Mazo, J A Pons
: Regulatory T cells (Tregs) play a potential role in operational tolerance in liver transplant patients, and microRNAs (miRNAs) are known to be involved in immunological responses and tolerance. Thus, we analyzed the implication of different peripheral blood Treg subsets and miRNAs on liver transplantation tolerance in 24 tolerant (Tol) and 23 non-tolerant (non-Tol) liver transplant recipients by cellular, genetic and epigenetic approximation. Non-Tol patients had a lower demethylation rate of the FOXP3 Treg-specific demethylated region (TSDR) than Tol patients that correlated with the frequency of circulating Tregs...
December 22, 2016: Liver Transplantation
https://www.readbyqxmd.com/read/27956762/tolerance-in-kidney-transplantation-what-is-on-the-b-side
#14
REVIEW
Laura Carreras-Planella, Francesc E Borràs, Marcella Franquesa
Regulatory B cells (Breg) are in the spotlight for their role in immune homeostasis maintenance and tolerance achievement as in the last years the correlation with functional and increased Breg numbers in autoimmune diseases and transplantation has been extensively proven. Their study is, however, in its infancy with still little knowledge and consensus on their origin, phenotype, and mechanism of action. All this hampers the pursuit of an effective Breg induction method for therapeutic purposes. In this review we aim to summarize the studies on human Breg and their implication in kidney transplantation and to further discuss the issues surrounding therapeutic applications of this cell subset...
2016: Mediators of Inflammation
https://www.readbyqxmd.com/read/27942862/altered-immune-reconstitution-of-b-and-t-cells-precedes-the-onset-of-clinical-symptoms-of-chronic-graft-versus-host-disease-and-is-influenced-by-the-type-of-onset
#15
E-M Bohmann, U Fehn, B Holler, D Weber, E Holler, W Herr, P Hoffmann, M Edinger, D Wolff
We analyzed lymphocyte subpopulations and cytokines 3 months after allogeneic hematopoietic stem cell transplantation aiming to identify predictive cellular and serum markers for chronic graft-versus-host disease (cGVHD). Samples of 49 patients (pts) (no cGVHD (n = 14), subsequent quiescent onset (n = 16), de novo onset of cGVHD (n = 19)) were analyzed in the absence of active GVHD by flow cytometry and enzyme-linked immunosorbent assay. All mean absolute cell counts are presented as cells per microliter; relative cell counts are presented as percentage of lymphocytes...
December 9, 2016: Annals of Hematology
https://www.readbyqxmd.com/read/27902485/impacts-of-cigarette-smoking-on-immune-responsiveness-up-and-down-or-upside-down
#16
REVIEW
Feifei Qiu, Chun-Ling Liang, Huazhen Liu, Yu-Qun Zeng, Shaozhen Hou, Song Huang, Xiaoping Lai, Zhenhua Dai
Cigarette smoking is associated with numerous diseases and poses a serious challenge to the current healthcare system worldwide. Smoking impacts both innate and adaptive immunity and plays dual roles in regulating immunity by either exacerbation of pathogenic immune responses or attenuation of defensive immunity. Adaptive immune cells affected by smoking mainly include T helper cells (Th1/Th2/Th17), CD4+CD25+ regulatory T cells, CD8+ T cells, B cells and memory T/B lymphocytes while innate immune cells impacted by smoking are mostly DCs, macrophages and NK cells...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27900346/preclinical-development-and-qualification-of-zfn-mediated-ccr5-disruption-in-human-hematopoietic-stem-progenitor-cells
#17
David L DiGiusto, Paula M Cannon, Michael C Holmes, Lijing Li, Anitha Rao, Jianbin Wang, Gary Lee, Philip D Gregory, Kenneth A Kim, Samuel B Hayward, Kathleen Meyer, Colin Exline, Evan Lopez, Jill Henley, Nancy Gonzalez, Victoria Bedell, Rodica Stan, John A Zaia
Gene therapy for HIV-1 infection is a promising alternative to lifelong combination antiviral drug treatment. Chemokine receptor 5 (CCR5) is the coreceptor required for R5-tropic HIV-1 infection of human cells. Deletion of CCR5 renders cells resistant to R5-tropic HIV-1 infection, and the potential for cure has been shown through allogeneic stem cell transplantation with naturally occurring homozygous deletion of CCR5 in donor hematopoietic stem/progenitor cells (HSPC). The requirement for HLA-matched HSPC bearing homozygous CCR5 deletions prohibits widespread application of this approach...
2016: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/27888331/the-origin-of-dcs-and-capacity-for-immunologic-tolerance-in-central-and-peripheral-tissues
#18
REVIEW
K Sanjana P Devi, Niroshana Anandasabapathy
Dendritic cells (DCs) are specialized immune sentinels that play key role in maintaining immune homeostasis by efficiently regulating the delicate balance between protective immunity and tolerance to self. Although DCs respond to maturation signals present in the surrounding milieu, multiple layers of suppression also co-exist that reduce the infringement of tolerance against self-antigens. These tolerance inducing properties of DCs are governed by their origin and a range of other factors including distribution, cytokines, growth factors, and transcriptional programing, that collectively impart suppressive functions to these cells...
November 25, 2016: Seminars in Immunopathology
https://www.readbyqxmd.com/read/27863545/porcine-treg-depletion-with-a-novel-diphtheria-toxin-based-anti-human-ccr4-immunotoxin
#19
Zhaohui Wang, Nalu Navarro-Alvarez, Jigesh A Shah, Huiping Zhang, Qi Huang, Qian Zheng, Joren C Madsen, David H Sachs, Christene A Huang, Zhirui Wang
Regulatory T cells (Tregs) are known to play an important role in immunoregulation and have been shown to facilitate induction of transplantation tolerance. Chemokine (C-C motif) receptor 4 (CCR4) is expressed on the surface of effector Tregs involved in controlling alloimmune and autoimmune responses. Recently we have developed a novel diphtheria-toxin based anti-human CCR4 immunotoxin for depleting CCR4(+) cells in vivo. In this study, we have demonstrated that the anti-human CCR4 immunotoxin bound to porcine lymphocytes including CD4(+)FoxP3(+) Tregs...
December 2016: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/27853649/cd24-blunts-oral-squamous-cancer-development-and-dampens-the-functional-expansion-of-myeloid-derived-suppressor-cells
#20
Caroline W Fugle, Yongliang Zhang, Feng Hong, Shaoli Sun, Caroline Westwater, Saleh Rachidi, Hong Yu, Elizabeth Garret-Mayer, Keith Kirkwood, Bei Liu, Zihai Li
CD24 expression has been implicated in the oncogenesis of multiple types of cancer and high tumor expression is considered a poor prognosis factor; however, the role of CD24 in oral cancer progression is unknown. Unlike other cancer types, we found that higher CD24 levels in human oral cancers are correlated to lower clinical stage and better overall survival. We then dissected the role of CD24 and mechanisms in oral cancer pathogenesis in mice using a genetic strategy and demonstrated that CD24 deficiency increased the oral cavity tumor burden in response to the carcinogen 4-nitroquioline 1-oxide (4-NQO)...
2016: Oncoimmunology
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