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Regulatory B cell in transplantation

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https://www.readbyqxmd.com/read/29352165/construction-of-full-length-japanese-reference-panel-of-class-i-hla-genes-with-single-molecule-real-time-sequencing
#1
Takahiro Mimori, Jun Yasuda, Yoko Kuroki, Tomoko F Shibata, Fumiki Katsuoka, Sakae Saito, Naoki Nariai, Akira Ono, Naomi Nakai-Inagaki, Kazuharu Misawa, Keiko Tateno, Yosuke Kawai, Nobuo Fuse, Atsushi Hozawa, Shinichi Kuriyama, Junichi Sugawara, Naoko Minegishi, Kichiya Suzuki, Kengo Kinoshita, Masao Nagasaki, Masayuki Yamamoto
Human leukocyte antigen (HLA) is a gene complex known for its exceptional diversity across populations, importance in organ and blood stem cell transplantation, and associations of specific alleles with various diseases. We constructed a Japanese reference panel of class I HLA genes (ToMMo HLA panel), comprising a distinct set of HLA-A, HLA-B, HLA-C, and HLA-H alleles, by single-molecule, real-time (SMRT) sequencing of 208 individuals included in the 1070 whole-genome Japanese reference panel (1KJPN). For high-quality allele reconstruction, we developed a novel pipeline, Primer-Separation Assembly and Refinement Pipeline (PSARP), in which the SMRT sequencing and additional short-read data were used...
January 19, 2018: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29348660/generation-and-characterization-of-alloantigen-specific-regulatory-t-cells-for-clinical-transplant-tolerance
#2
James M Mathew, Jessica H Voss, Scott T McEwen, Iwona Konieczna, Arjun Chakraborty, Xuemei Huang, Jie He, Lorenzo Gallon, Richard S Kornbluth, Joseph R Leventhal
Donor-specific CD4+CD127-CD25+FOXP3+ regulatory T cells (AgTregs) have the potential to induce clinical transplant tolerance; however, their expansion ex vivo remains challenging. We optimized a novel expansion protocol to stimulate donor-specific Tregs using soluble 4-trimer CD40 ligand (CD40L)-activated donor B cells that expressed mature antigen-presenting cell markers. This avoided the use of CD40L-expressing stimulator cells that might otherwise result in potential cellular contamination. Purified allogeneic "recipient" CD4+CD25+ Tregs were stimulated on days 0 and 7 with expanded "donor" B cells in the presence of IL-2, TGFβ and sirolimus (SRL)...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29338551/the-regulatory-roles-of-b-cell-subsets-in-transplantation
#3
Zhulang Chu, Weilong Zou, Yanan Xu, Qiquan Sun, Yong Zhao
B cells mediate allograft rejection through antigen presentation, and production of cytokines and antibodies. More and more immunosuppressive agents specifically targeting B cells and plasma cells have been applied in clinical transplantation. However, recent studies have indicated the regulatory roles of B cells. Therefore, it is vital to clarify the different effects of B cell subsets in organ transplantation so that we can completely understand the diverse functions of B cells in transplantation. Areas covered: This review focuses on the regulatory roles of B cells in transplantation...
January 17, 2018: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/29338084/importance-of-b-cells-to-development-of-tregs-and-prolongation-of-tissue-allograft-survival-in-recipients-receiving-autologous-bone-marrow-transplantation
#4
Reginald M Gorczynski, Kaveh Farrokhi, Christopher Gorczynski, Hassan Sadozai, Fang Zhu, Ismat Khatri
We previously showed that congenic bone marrow transplantation (BMTx) post myeloablation augmented tissue allograft survival in association with increased Tregs of both host and bone marrow donor origin. Regulatory B cells (Bregs) can also modulate T cell immunity and B cells may be implicated in the development of Tregs. Accordingly, we explored the effect of B cell depletion in vivo on augmented graft survival post BMTx. C57BL/6 mice received BALB/c skin allografts followed 7d later by myeloablation using cyclophosphamide and busulphan...
January 16, 2018: Immunology
https://www.readbyqxmd.com/read/29326088/age-effects-of-distinct-immune-checkpoint-blockade-treatments-in-a-mouse-melanoma-model
#5
Álvaro Padrón, Vincent Hurez, Harshita B Gupta, Curtis A Clark, Sri Lakshmi Pandeswara, Bin Yuan, Robert S Svatek, Mary Jo Turk, Justin M Drerup, Rong Li, Tyler J Curiel
Cancer immunotherapy has shown remarkable recent progress. Immune checkpoint blocking antibodies have become the most successful anti-cancer agent class ever developed, with six distinct agents approved since 2011 for a wide variety of cancers. Although age is the biggest risk factor for cancer (aside from selected early-onset pediatric cancers), these agents were tested pre-clinically in young hosts, and there is remarkably little published on the effects of host age on treatment outcomes in pre-clinical studies or human clinical trials...
January 8, 2018: Experimental Gerontology
https://www.readbyqxmd.com/read/29300231/long-term-nonhuman-primate-renal-allograft-survival-without-ongoing-immunosuppression-in-recipients-of-delayed-donor-bone-marrow-transplantation
#6
Kiyohiko Hotta, Tetsu Oura, Abbas Dehnadi, Svjetlan Boskovic, Masatoshi Matsunami, Ivy Rosales, Rex N Smith, Robert B Colvin, A Benedict Cosimi, Tatsuo Kawai
BACKGROUND: We have previously reported successful induction of renal allograft tolerance in nonhuman primates (NHP) following an initial posttransplant period of conventional immunosuppression (delayed tolerance) using a nonmyeloablative conditioning regimen consisting of anti-CD154 and anti-CD8 mAbs plus equine ATG (Atgam) and donor bone marrow transplantation (DBMT). Since these reagents are not currently clinically available, the protocol was revised to be applicable to human recipients of deceased donor allografts...
January 4, 2018: Transplantation
https://www.readbyqxmd.com/read/29221684/ex-vivo-flush-of-the-limb-allograft-reduces-inflammatory-burden-prior-to-transplantation
#7
Kavit R Amin, Alexandra L Ball, Chandanpreet Chhina, Rebecca J Edge, John P Stone, William R Critchley, Jason K Wong, James E Fildes
BACKGROUND: Passenger leucocytes and inflammatory debris transferred from the donor limb to the recipient can induce allorecognition, which activates the host immune response. This is the first study to evaluate whether the transfer of this inflammatory burden can be reduced via post-preservation flush prior to revascularisation, and whether this is influenced by ischaemia. METHODS: Bilateral forelimbs from the same pig were procured and infused with preservation flush and stored on ice...
November 24, 2017: Journal of Plastic, Reconstructive & Aesthetic Surgery: JPRAS
https://www.readbyqxmd.com/read/29217821/il-11-promotes-the-treatment-efficacy-of-hematopoietic-stem-cell-transplant-therapy-in-aplastic-anemia-model-mice-through-a-nf-%C3%AE%C2%BAb-microrna-204-thrombopoietin-regulatory-axis
#8
Yan Wang, Zhi-Yun Niu, Yu-Jie Guo, Li-Hua Wang, Feng-Ru Lin, Jing-Yu Zhang
Hematopoietic stem cell (HSC) transplantation could be of therapeutic value for aplastic anemia (AA) patients, and immunosuppressants may facilitate the efficiency of the procedure. As anti-inflammatory cytokine interleukin-11 (IL-11) has a thrombopoietic effect, its use in cases of chronic bone marrow failure, such as AA, has been proposed to induce HSC function. However, the putative mechanisms that may support this process remain poorly defined. We found that decreased miR-204-5p levels were coincident with increased proliferation in mouse HSCs following exposure to IL-11 in vitro...
December 8, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29217299/high-pd-l1-cd86-mfi-ratio-and-il-10-secretion-characterize-human-regulatory-dendritic-cells-generated-for-clinical-testing-in-organ-transplantation
#9
Alan F Zahorchak, Camila Macedo, David E Hamm, Lisa H Butterfield, Diana M Metes, Angus W Thomson
Human regulatory dendritic cells (DCreg) were generated from CD14 immunobead-purified or elutriated monocytes in the presence of vitamin D3 and IL-10. They exhibited similar, low levels of costimulatory CD80 and CD86, but comparatively high levels of co-inhibitory programed death ligand-1 (PD-L1) and IL-10 production compared to control immature DC (iDC). Following Toll-like receptor 4 ligation, unlike control iDC, DCreg resisted phenotypic and functional maturation and further upregulated PD-L1:CD86 expression...
September 14, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/29215459/complete-b-cell-deficiency-reduces-allograft-inflammation-and-intragraft-macrophages-a-rat-kidney-transplant-model
#10
Sarah E Panzer, Nancy A Wilson, Bret M Verhoven, Ding Xiang, C Dustin Rubinstein, Robert R Redfield, Weixiong Zhong, Shannon R Reese
BACKGROUND: Increasingly it is being appreciated that B cells have broad roles beyond the humoral response, and are able to contribute to and regulate inflammation. The specific role of B cells in the pathogenesis of early allograft inflammation remains unclear. METHODS: To address this question, we generated B cell deficient Lewis rats via CRISPR technology. In a full mismatch transplant model, kidneys from Brown Norway donors were transplanted into B cell deficient Lewis recipients (B) or wild type Lewis recipients...
December 5, 2017: Transplantation
https://www.readbyqxmd.com/read/29212210/mir-21-silencing-ameliorates-experimental-autoimmune-encephalomyelitis-by-promoting-the-differentiation-of-il-10-producing-b-cells
#11
Hui Wang, Wenrong Xu, Qixiang Shao, Qing Ding
IL-10-producing regulatory B (IL-10+ Breg) cells promote tolerance in autoimmune diseases and transplantation. However, it remains unclear whether microRNAs are involved in the development of IL-10+ Breg cells. Here, we found that microRNA-21 (miR-21) acts as an upstream regulator of IL-10 by targeting the 3' untranslated region of IL-10 mRNA. We also demonstrated that IL-10+ Breg cells exhibit lower miR-21 expression than non-Breg cells and that miR-21 acts as a potent negative regulator of the differentiation of IL-10+ Breg cells...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29198869/the-ratio-of-circulating-regulatory-cluster-of-differentiation-4-t-cells-to-endothelial-progenitor-cells-predicts-clinically-significant-acute-rejection-after-heart-transplantation
#12
Dong-Hyun Choi, Stephen A Chmura, Vasavi Ramachandran, Kira Y Dionis-Petersen, Yuhei Kobayashi, Takeshi Nishi, Helen Luikart, Sadia Dimbil, Jon Kobashigawa, Kiran Khush, David B Lewis, William F Fearon
BACKGROUND: The aim of this study was to determine the value of the ratio of the percentage of circulating regulatory cluster of differentiation 4 T cells (%Tregs) to the percentage of endothelial progenitor cells (%EPCs; Treg/EPC ratio) for predicting clinically significant acute rejection. METHODS: Peripheral blood %Tregs and %EPCs were quantified in 91 cardiac transplant recipients using flow cytometry at a mean of 42 ± 13 days after transplant. The primary end point was clinically significant acute rejection, defined as an event that led to an acute augmentation of immunosuppression in conjunction with an International Society for Heart and Lung Transplantation grade ≥ 2R in a right ventricular endomyocardial biopsy specimen or non-cellular rejection (specimen-negative rejection) with hemodynamic compromise (decrease in left ventricular ejection fraction by > 25%)...
October 22, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/29189411/diverse-roles-of-tim4-in-immune-activation-implications-for-alloimmunity
#13
Martina M McGrath
PURPOSE OF REVIEW: T-cell immunoglobulin and mucin domain-containing molecule (TIM)4 is a costimulatory molecule and phosphatidylserine receptor. Its dominant function varies according to the expressing cell and site of activation. In recent years, studies have identified its role in diverse disease processes and increasingly in alloimmunity. Herein, we will comprehensively review the literature on TIM4 and outline its function in shaping the alloimmune response. RECENT FINDINGS: TIM4 expression on dendritic cells increases following transplantation...
November 20, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/29126177/cd30-expression-in-monomorphic-posttransplant-lymphoproliferative-disorder-diffuse-large-b-cell-lymphoma-correlates-with-greater-regulatory-t-cell-infiltration
#14
Christopher Hartley, James W Vaughan, Jason Jarzembowski, Steven H Kroft, Paul Hosking, Alexandra M Harrington, Horatiu Olteanu
Objectives: CD30 is a protein thought to promote cell proliferation/survival and downregulate the immune response. Twenty percent to 40% of de novo diffuse large B-cell lymphomas (DLBCLs) express CD30, and some patients have been treated with the anti-CD30 agent brentuximab. In the solid organ transplant setting, allograft regulatory T cells (Tregs) have been shown to be modulated via CD30 signaling. Methods: Posttransplant lymphoproliferative disorders (PTLDs) constitute a heterogeneous group of lymphomas, and since CD30 expression has been rarely formally assessed in PTLDs, we analyzed a cohort of PTLDs...
November 20, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/29111199/density-dependent-re-tuning-of-autoreactive-t-cells-alleviates-their-pathogenicity-in-a-lymphopenic-environment
#15
Eleanore Chuang, Marilyn Augustine, Matthew Jung, Ronald H Schwartz, Nevil J Singh
Peripheral T cell tolerance is challenging to induce in partially lymphopenic hosts and this is relevant for clinical situations involving transplant tolerance. While the shortage of regulatory cells is thought to be one reason for this, T cell-intrinsic tolerance processes such as anergy are also poorly triggered in such hosts. In order to understand the latter, we used a T cell deficient mouse model system where adoptively transferred autoreactive T cells are significantly tolerized in a cell intrinsic fashion, without differentiation to regulatory T cells...
December 2017: Immunology Letters
https://www.readbyqxmd.com/read/29093262/human-regulatory-t-cells-undergo-self-inflicted-damage-via-granzyme-pathways-upon-activation
#16
Esilida Sula Karreci, Siawosh K Eskandari, Farokh Dotiwala, Sujit K Routray, Ahmed T Kurdi, Jean Pierre Assaker, Pavlo Luckyanchykov, Albana B Mihali, Omar Maarouf, Thiago J Borges, Abdullah Alkhudhayri, Kruti R Patel, Amr Radwan, Irene Ghobrial, Martina McGrath, Anil Chandraker, Leonardo V Riella, Wassim Elyaman, Reza Abdi, Judy Lieberman, Jamil Azzi
Tregs hold great promise as a cellular therapy for multiple immunologically mediated diseases, given their ability to control immune responses. The success of such strategies depends on the expansion of healthy, suppressive Tregs ex vivo and in vivo following the transfer. In clinical studies, levels of transferred Tregs decline sharply in the blood within a few days of the transfer. Tregs have a high rate of apoptosis. Here, we describe a new mechanism of Treg self-inflicted damage. We show that granzymes A and -B (GrA and GrB), which are highly upregulated in human Tregs upon stimulation, leak out of cytotoxic granules to induce cleavage of cytoplasmic and nuclear substrates, precipitating apoptosis in target cells...
November 2, 2017: JCI Insight
https://www.readbyqxmd.com/read/29068389/clinical-effect-of-irt-5-probiotics-on-immune-modulation-of-autoimmunity-or-alloimmunity-in-the-eye
#17
Jaeyoung Kim, Se Hyun Choi, Yu Jeong Kim, Hyun Jeong Jeong, Jin Suk Ryu, Hyun Ju Lee, Tae Wan Kim, Sin-Hyeog Im, Joo Youn Oh, Mee Kum Kim
BACKGROUND: Although the relation of the gut microbiota to a development of autoimmune and inflammatory diseases has been investigated in various animal models, there are limited studies that evaluate the effect of probiotics in the autoimmune eye disease. Therefore, we aimed to investigate the effect of IRT-5 probiotics consisting of Lactobacillus casei, Lactobacillus acidophilus, Lactobacillus reuteri, Bifidobacterium bifidum, and Streptococcus thermophilus on the autoimmunity of uveitis and dry eye and alloimmunity of corneal transplantation...
October 25, 2017: Nutrients
https://www.readbyqxmd.com/read/29038423/regulation-of-t-cell-alloimmunity-by-pi3k%C3%AE-and-pi3k%C3%AE
#18
Mayuko Uehara, Martina M McGrath, Shunsuke Ohori, Zhabiz Solhjou, Naima Banouni, Sujit Routray, Catherine Evans, Jonathan P DiNitto, Abdallah Elkhal, Laurence A Turka, Terry B Strom, Stefan G Tullius, David G Winkler, Jamil Azzi, Reza Abdi
Phosphatidylinositol-3-kinases (PI3K) γ and δ are preferentially enriched in leukocytes, and defects in these signaling pathways have been shown to impair T cell activation. The effects of PI3Kγ and PI3Kδ on alloimmunity remain underexplored. Here, we show that both PI3Kγ -/- and PI3Kδ D910A/D910A mice receiving heart allografts have suppression of alloreactive T effector cells and delayed acute rejection. However, PI3Kδ mutation also dampens regulatory T cells (Treg). After treatment with low dose CTLA4-Ig, PI3Kγ -/- , but not PI3Κδ D910A/D910A , recipients exhibit indefinite prolongation of heart allograft survival...
October 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29023267/enhanced-th17-responses-in-patients-with-il10-receptor-deficiency-and-infantile-onset-ibd
#19
Dror S Shouval, Liza Konnikova, Alexandra E Griffith, Sarah M Wall, Amlan Biswas, Lael Werner, Moran Nunberg, Jochen Kammermeier, Jeremy A Goettel, Rajsavi Anand, Hannah Chen, Batia Weiss, Jian Li, Anthony Loizides, Baruch Yerushalmi, Tadahiro Yanagi, Rita Beier, Laurie S Conklin, Christen L Ebens, Fernanda G M S Santos, Mary Sherlock, Jeffery D Goldsmith, Daniel Kotlarz, Sarah C Glover, Neil Shah, Athos Bousvaros, Holm H Uhlig, Aleixo M Muise, Christoph Klein, Scott B Snapper
BACKGROUND: IL10 receptor (IL10R) deficiency causes severe infantile-onset inflammatory bowel disease. Intact IL10R-dependent signals have been shown to be important for innate and adaptive immune cell functions in mice. We have previously reported a key role of IL10 in the generation and function of human anti-inflammatory macrophages. Independent of innate immune cell defects, the aim of the current study was to determine the role of IL10R signaling in regulating human CD4 T-cell function...
November 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28983300/human-tregs-made-antigen-specific-by-gene-modification-the-power-to-treat-autoimmunity-and-antidrug-antibodies-with-precision
#20
REVIEW
Patrick R Adair, Yong Chan Kim, Ai-Hong Zhang, Jeongheon Yoon, David W Scott
Human regulatory CD4(+) T cells (Tregs) are potent immunosuppressive lymphocytes responsible for immune tolerance and homeostasis. Since the seminal reports identifying Tregs, vast research has been channeled into understanding their genesis, signature molecular markers, mechanisms of suppression, and role in disease. This research has opened the doors for Tregs as a potential therapeutic for diseases and disorders such as multiple sclerosis, type I diabetes, transplantation, and immune responses to protein therapeutics, like factor VIII...
2017: Frontiers in Immunology
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