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Regulatory B cell in transplantation

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https://www.readbyqxmd.com/read/28434942/ipsc-derived-regulatory-dendritic-cells-inhibit-allograft-rejection-by%C3%A2-generating-alloantigen-specific-regulatory-t-cells
#1
Songjie Cai, Jiangang Hou, Masayuki Fujino, Qi Zhang, Naotsugu Ichimaru, Shiro Takahara, Ryoko Araki, Lina Lu, Ji-Mei Chen, Jian Zhuang, Ping Zhu, Xiao-Kang Li
Regulatory dendritic cell (DCregs)-based immunotherapy is a potential therapeutic tool for transplant rejection. We generated DCregs from murine induced pluripotent stem cells (iPSCs), which could remain in a "stable immature stage" even under strong stimulation. Harnessing this characteristic, we hypothesized that iPS-DCregs worked as a negative vaccine to generate regulatory T cells (Tregs), and induced donor-specific allograft acceptance. We immunized naive CBA (H-2K(k)) mice with B6 (H-2K(b)) iPS-DCregs and found that Tregs (CD4(+)CD25(+)FOXP3(+)) significantly increased in CBA splenocytes...
April 18, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28415669/micro-rna-98-suppresses-interleukin-10-in-peripheral-b-cells-in-patient-post-cardio-transplantation
#2
Jiangping Song, Wenjun Su, Xiao Chen, Qian Zhao, Ningning Zhang, Mao-Gang Li, Ping-Chang Yang, Liqing Wang
The immune tolerance to the transplant heart survival is critical. Regulatory B cells are one of the major immune regulatory cell populations in the immune tolerance. Micro RNAs (miR) can regulate the activities of immune cells, such as the expression of interleukin (IL)-10 by B cells. This study tests a hypothesis that micro RNA (miR)-98 plays a role in the regulation of interleukin (IL)-10 expression in B cells (B10 cell) after heart transplantation. In this study, the peripheral blood samples were collected from patients before and after heart transplantation...
March 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28405514/regulatory-b-cells-promote-graft-versus-host-disease-prevention-and-maintain-graft-versus-leukemia-activity-following-allogeneic-bone-marrow-transplantation
#3
Yue Hu, Gan-Lin He, Xiang-Yu Zhao, Xiao-Su Zhao, Yu Wang, Lan-Ping Xu, Xiao-Hui Zhang, Xue-Zhong Yu, Kai-Yan Liu, Ying-Jun Chang, Xiao-Jun Huang
Regulatory B cells (Bregs) are involved in the pathogenesis of graft-versus-host disease (GVHD). However, whether Bregs can alleviate acute GVHD without compromising graft-versus-leukemia (GVL) effects remains unclear. Here, we evaluated the role of Bregs in acute GVHD and GVL activity in both a mouse model and a clinical cohort study. In the acute GVHD mouse model, co-transplantation of Bregs prevents onset through inhibiting Th1 and Th17 differentiation and expanding regulatory T cells. In the GVL mouse model, Bregs contributed to the suppression of acute GVHD but had no adverse effect on GVL activity...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28403126/effector-antitumor-and-regulatory-t-cell-responses-influence-the-development-of-nonmelanoma-skin-cancer-in-kidney-transplant-patients
#4
Elena Crespo, Loreto Fernandez, Marc Lúcia, Edoardo Melilli, Ricardo Lauzurica, Rosa Maria Penin, Ariadna Quer, Sergio Luque, Maria Quero, Anna Manonelles, Joan Torras, Josep Maria Cruzado, Laura Cañas, Josep Maria Grinyó, Oriol Bestard
BACKGROUND: Chronic immunosuppression promotes Nonmelanocytic Squamous Cell Carcinoma (SCC) after kidney transplantation. Adaptive and innate immunity play a key role controlling tumor growth and are influenced by different immunosuppressive agents. We hypothesized that functional impairment of tumor-specific T cell responses due to CNI could contribute to SCC development, whereas conversion to mTOR-i could recover this protective immune response. METHODS: Peripheral tumor-specific T cell responses against main SCC-derived antigens using the IFN-γ ELISPOT assay and intratumor and circulating immune phenotypes (CD4+T, CD8+T, CD20+B, CD56+NK, FOXP3+Tregs) were explored in a cross-sectional analysis in 59 kidney transplant patients with SCC on CNI (KT-CNI-SCC) or mTOR-i (KT-mTORi-SCC), 25 nontransplants developing SCC (NoKT-SCC) and 6 healthy controls...
April 11, 2017: Transplantation
https://www.readbyqxmd.com/read/28402253/immunoregulatory-role-of-b-lymphocytes-in-alloresponse-to-kidney-transplant
#5
Tomasz Baran, Maria Boratyńska
B cells are a group of diverse phenotype and function subsets, which can both stimulate and inhibit the immune response to an allograft. They participate in the rejection process by influencing differentiation, proliferation and effector functions of T lymphocytes. B cells injure the graft via the ADCC (antibody-dependent cellular cytotoxicity) reaction and humoral rejection through plasmocyte production of donor-specific antibodies. A converse, suppressive mode of B cells can attribute to the development of tolerance and protect the graft from rejection...
April 12, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28368375/multiple-myeloma-patients-in-long-term-complete-response-after-autologous-stem-cell-transplantation-express-a-particular-immune-signature-with-potential-prognostic-implication
#6
A Arteche-López, A Kreutzman, A Alegre, P Sanz Martín, B Aguado, M González-Pardo, M Espiño, L M Villar, D García Belmonte, R de la Cámara, C Muñoz-Calleja
The proportion of multiple myeloma patients in long-term complete response (LTCR-MM) for more than 6 years after autologous stem cell transplantation (ASCT) is small. To evaluate whether this LTCR is associated with a particular immune signature, peripheral blood samples from 13 LTCR-MM after ASCT and healthy blood donors (HBD) were analysed. Subpopulations of T-cells (naïve, effector, central memory and regulatory), B-cells (naïve, marginal zone-like, class-switched memory, transitional and plasmablasts) and NK-cells expressing inhibitory and activating receptors were quantified by multiparametric flow cytometry (MFC)...
April 3, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28362427/anti-apoptotic-proteins-bcl-2-mcl-1-and-a1-summate-collectively-to-maintain-survival-of-immune-cell-populations-both-in-vitro-and-in-vivo
#7
Emma M Carrington, Yifan Zhan, Jamie L Brady, Jian-Guo Zhang, Robyn M Sutherland, Natasha S Anstee, Robyn L Schenk, Ingela B Vikstrom, Rebecca B Delconte, David Segal, Nicholas D Huntington, Philippe Bouillet, David M Tarlinton, David Cs Huang, Andreas Strasser, Suzanne Cory, Marco J Herold, Andrew M Lew
Survival of various immune cell populations has been proposed to preferentially rely on a particular anti-apoptotic BCL-2 family member, for example, naive T cells require BCL-2, while regulatory T cells require MCL-1. Here we examined the survival requirements of multiple immune cell subsets in vitro and in vivo, using both genetic and pharmacological approaches. Our findings support a model in which survival is determined by quantitative participation of multiple anti-apoptotic proteins rather than by a single anti-apoptotic protein...
March 31, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28360016/fc%C3%AE-riib-expression-on-b-cells-is-associated-with-treatment-efficacy-for-acute-rejection-after-kidney-transplantation
#8
Juan Jin, Jianguang Gong, Bo Lin, Yiwen Li, Qiang He
BACKGROUND: Fcγ receptors (FcγR) play a role in the acute rejection (AR) of organ transplants. FcγRIIB is an inhibitory FcγR expressed on B cells. Intravenous IgG (IVIG) and CD28 monoclonal antibody (mAb) have been shown to have immunomodulatory properties against AR. AIM: To examine the association between FcγRIIB expression on B cell subpopulations and AR treatment efficacy. METHODS: Male F344 rats were used as kidney donors and Lewis rats as recipients to establish models of renal transplantation...
March 27, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28352104/helminth-induced-alterations-of-the-gut-microbiota-exacerbate-bacterial-colitis
#9
C Su, L Su, Y Li, S R Long, J Chang, W Zhang, W A Walker, R J Xavier, B J Cherayil, H N Shi
Infection with the intestinal helminth parasite Heligmosomoides polygyrus exacerbates the colitis caused by the bacterial enteropathogen Citrobacter rodentium. To clarify the underlying mechanism, we analyzed fecal microbiota composition of control and helminth-infected mice and evaluated the functional role of compositional differences by microbiota transplantation experiments. Our results showed that infection of Balb/c mice with H. polygyrus resulted in significant changes in the composition of the gut microbiota, characterized by a marked increase in the abundance of Bacteroidetes and decreases in Firmicutes and Lactobacillales...
March 29, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28321218/the-induction-and-maintenance-of-transplant-tolerance-engages-both-regulatory-and-anergic-cd4-t-cells
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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