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Regulatory B cell in transplantation

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https://www.readbyqxmd.com/read/28321218/the-induction-and-maintenance-of-transplant-tolerance-engages-both-regulatory-and-anergic-cd4-t-cells
#1
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/28302753/erythropoietin-receptor-mediated-molecular-crosstalk-promotes-t-cell-immunoregulation-and-transplant-survival
#2
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/28296255/breg-dependent-islet-transplant-tolerance-is-also-nk-cell-dependent
#3
Christian Schuetz, Kang Mi Lee, Ryan Scott, Lisa Kojima, Laura Washburn, Liye Liu, Wei-Hui Liu, Haley Tector, Ji Lei, Heidi Yeh, James Kim, James F Markmann
Immunologic tolerance to solid organ and islet cell grafts has been achieved in various rodent models using antibodies directed at CD45RB and Tim-1. We have shown that this form of tolerance depends on regulatory B-cells. To elucidate further the mechanism by which Bregs induce tolerance we investigated the requirement of NK and NKT cells in this model. To do so, hyperglycemic B6, μMT, Beige or CD1d(-/-) mice received Balb/c islet grafts and treatment with the tolerance inducing regimen consisting of anti-CD45RB and anti -TIM1...
March 10, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28296027/transitional-b-cells-predominantly-reconstituted-after-a-desensitization-therapy-using-rituximab-before-kidney-transplantation
#4
Masako Ikemiyagi, Toshihito Hirai, Rumi Ishii, Satoshi Miyairi, Masayoshi Okumi, Kazunari Tanabe
The role of B cells in graft rejection and tolerance has aroused great interest. We previously reported that rituximab (RIT) induction prior to kidney transplantation (KTx) reduced the incidence rate of chronic rejection. Here, we performed a cross sectional investigation to determine the characteristics of B cells after RIT induction for KTx. We sampled blood from 29 patients with (N = 16) and without (N = 13) RIT induction 3 to 18 months after KTx. In the RIT group, the majority of repopulating B cells was the transitional type, while memory B cells were scarce...
March 13, 2017: Therapeutic Apheresis and Dialysis
https://www.readbyqxmd.com/read/28289675/humoral-immunodeficiency-with-hypotonia-feeding-difficulties-enteropathy-and-mild-eczema-caused-by-a-classical-foxp3-mutation
#5
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/28275376/immunological-balance-is-associated-with-clinical-outcome-after-autologous-hematopoietic-stem-cell-transplantation-in-type-1-diabetes
#6
Kelen C R Malmegrim, Júlia T C de Azevedo, Lucas C M Arruda, Joana R F Abreu, Carlos E B Couri, Gislane L V de Oliveira, Patricia V B Palma, Gabriela T Scortegagna, Ana B P L Stracieri, Daniela A Moraes, Juliana B E Dias, Fabiano Pieroni, Renato Cunha, Luiza Guilherme, Nathália M Santos, Milton C Foss, Dimas T Covas, Richard K Burt, Belinda P Simões, Júlio C Voltarelli, Bart O Roep, Maria C Oliveira
Autologous hematopoietic stem cell transplantation (AHSCT) increases C-peptide levels and induces insulin independence in patients with type 1 diabetes. This study aimed to investigate how clinical outcomes may associate with the immunological status, especially concerning the balance between immunoregulation and autoreactivity. Twenty-one type 1 diabetes patients were monitored after AHSCT and assessed every 6 months for duration of insulin independence, C-peptide levels, frequencies of islet-specific autoreactive CD8(+) T cells (CTL), regulatory lymphocyte subsets, thymic function, and T-cell repertoire diversity...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28270364/new-frontiers-in-the-therapy-of-primary-immunodeficiency-from-gene-addition-to-gene-editing
#7
REVIEW
Donald B Kohn, Caroline Y Kuo
The most severe primary immune deficiency diseases (PIDs) have been successfully treated with allogeneic hematopoietic stem cell transplantation for more than 4 decades. However, such transplantations have the best outcomes when there is a well-matched donor available because immune complications, such as graft-versus-host disease, are greater without a matched sibling donor. Gene therapy has been developed as a method to perform autologous transplantations of a patient's own stem cells that are genetically corrected...
March 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28261223/regulatory-b-cells-in-pregnancy-lessons-from-autoimmunity-graft-tolerance-and-cancer
#8
REVIEW
Ruth Marian Guzman-Genuino, Kerrilyn R Diener
The success of pregnancy is contingent on the maternal immune system recognizing and accommodating a growing semi-allogeneic fetus. Specialized subsets of lymphocytes capable of negative regulation are fundamental in this process, and include the regulatory T cells (Tregs) and potentially, regulatory B cells (Bregs). Most of our current understanding of the immune regulatory role of Bregs comes from studies in the fields of autoimmunity, transplantation tolerance, and cancer biology. Bregs control autoimmune diseases and can elicit graft tolerance by inhibiting the differentiation of effector T cells and dendritic cells (DCs), and activating Tregs...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28257995/regulatory-b-cells-phenotype-function-and-role-in-transplantation
#9
REVIEW
C M Wortel, S Heidt
While B cells are traditionally known for their roles in antibody production, antigen presentation and cytokine production, recent studies have highlighted the existence of B cells with regulatory properties, which have been termed Bregs, analogous to regulatory T cells (Tregs). Bregs have been found to play a role in autoimmune disease, malignancies, infections, and may also be involved in solid organ transplantation. Their main mechanism of action is by promoting the development of Tregs while suppressing effector CD4(+) and CD8(+) T cells, primarily by IL-10 secretion...
March 1, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28257450/differential-depletion-of-total-t-cells-and-regulatory-t-cells-and-prolonged-allotransplant-survival-in-cd3%C3%A6-humanized-mice-treated-with-polyclonal-anti-human-thymocyte-globulin
#10
Maja Buszko, Benno Cardini, Rupert Oberhuber, Lukas Oberhuber, Bojana Jakic, Anja Beierfuss, Georg Wick, Giuseppe Cappellano
Thymoglobulin (ATG) is a polyclonal rabbit antibody against human thymocytes used as a T cell-depleting agent to prevent or treat allotransplant rejection. The aim of the present study was to investigate the effect of low dose ATG treatment exclusively on T cells using a humanized BALB/c human CD3Ɛ transgenic mouse model expressing both human and murine T cell receptors (TCR). Mice received a single intravenous (i.v.) injection of ATG. Blood and peripheral lymphoid organs were obtained after different time points...
2017: PloS One
https://www.readbyqxmd.com/read/28241095/immune-checkpoint-inhibitors-in-challenging-populations
#11
REVIEW
Douglas B Johnson, Ryan J Sullivan, Alexander M Menzies
Immune checkpoint inhibitors, including those targeting the programmed cell death 1/programmed cell death ligand 1 and cytotoxic T lymphocyte antigen 4 pathways, are revolutionizing cancer therapeutics. Both activity and toxicities largely stem from unleashing tumor- or host-specific cytotoxic T cells. Many patients seen in routine clinical practice have not qualified for or have been seriously underrepresented in immune checkpoint inhibitor clinical trials. Thus, a major gap in knowledge regarding the safety and efficacy of these agents persists in many populations, even after regulatory approval...
February 27, 2017: Cancer
https://www.readbyqxmd.com/read/28219835/marked-in-vivo-donor-regulatory-t-cell-expansion-via-interleukin-2-and-tl1a-ig-stimulation-ameliorates-graft-versus-host-disease-but-preserves-graft-versus-leukemia-in-recipients-after-hematopoietic-stem-cell-transplantation
#12
Dietlinde Wolf, Henry Barreras, Cameron S Bader, Sabrina Copsel, Casey O Lightbourn, Brent J Pfeiffer, Norman H Altman, Eckhard R Podack, Krishna V Komanduri, Robert B Levy
Regulatory T cells (Tregs) are critical for self-tolerance. Although adoptive transfer of expanded Tregs limits graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT), ex vivo generation of large numbers of functional Tregs remains difficult. Here, we demonstrate that in vivo targeting of the TNF superfamily receptor TNFRSF25 using the TL1A-Ig fusion protein, along with IL-2, resulted in transient but massive Treg expansion in donor mice, which peaked within days and was nontoxic...
February 20, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28219834/incidence-and-outcomes-of-central-nervous-system-hemophagocytic-lymphohistiocytosis-relapse-after-reduced-intensity-conditioning-hematopoietic-stem-cell-transplantation
#13
Dana T Lounder, Pooja Khandelwal, Sharat Chandra, Michael B Jordan, Ashish R Kumar, Michael Grimley, Stella M Davies, Jack J Bleesing, Rebecca A Marsh
Hemophagocytic lymphohistiocytosis (HLH) is an immune regulatory disorder that commonly presents with central nervous system (CNS) involvement. The only cure for genetic HLH is hematopoietic stem cell transplantation (HSCT), typically treated with reduced-intensity conditioning (RIC) regimens. We sought to estimate the incidence of CNS relapse after RIC HSCT, determine risk factors, and evaluate outcomes. We performed a retrospective chart review of 94 consecutive children and young adults with primary HLH who received RIC HSCT...
February 17, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28219580/use-of-anti-thymocyte-globulin-for-induction-therapy-in-cardiac-transplantation-a-review
#14
V Ruan, L S C Czer, M Awad, M Kittleson, J Patel, F Arabia, F Esmailian, D Ramzy, J Chung, M De Robertis, A Trento, J A Kobashigawa
The most common causes of death after heart transplantation (HTx) include acute rejection and multi-organ failure in the early period and malignancy and cardiac allograft vasculopathy (CAV) in the late period. Polyclonal antibody preparations such as rabbit anti-thymocyte globulin (ATG) may reduce early acute rejection and the later occurrence of CAV after HTx. ATG therapy depletes T cells, modulates adhesion and cell-signaling molecules, interferes with dendritic cell function, and induces B-cell apoptosis and regulatory and natural killer T-cell expansion...
March 2017: Transplantation Proceedings
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
#15
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/28122485/validation-of-donor-specific-tolerance-of-intestinal-transplant-by-a-secondary-heart-transplantation-model
#16
Wang Pengcheng, Li Xiaosong, Li Xiaofeng, Li Zhongzhi
OBJECTIVES: It is well accepted that survival after a second organ transplant without immunosuppressive agents indicates tolerance for the first transplant. To validate donor-specific tolerance, we established a rat model with a secondary heart transplant after intestinal transplant, which has so far not been described in the literature. MATERIALS AND METHODS: We transplanted intestine from Fischer F344 rats to Lewis rats orthotopically. Lewis rats received tacrolimus pretreatment before transplant and a 14-day course of rapamycin 1 month after transplant...
February 2017: Experimental and Clinical Transplantation
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
#17
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
#18
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
#19
REVIEW
A S Chong, S H Khiew
Establishing a state of transplantation tolerance that leads to indefinite graft survival without the need for lifelong immunosuppression has been achieved successfully 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-nonhuman-primate-renal-allograft-rejection
#20
S C Kim, W Wakwe, L B Higginbotham, D V Mathews, C P Breeden, A C Stephenson, J Jenkins, E Strobert, K Price, L Price, R Kuhn, H Wang, A Yamniuk, S Suchard, A B Farris, T C Pearson, C P Larsen, M L Ford, A Suri, S Nadler, A 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
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