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bone marrow transplantation, immunology

Yifeng Cai, Shoubao Ma, Yuejun Liu, Huanle Gong, Qiao Cheng, Bo Hu, Yan Wu, Xiao Yu, Chen Dong, Kai Sun, Depei Wu, Haiyan Liu
The role of IL-17 and IL-17-producing CD4(+) T cells in acute graft-versus-host disease (GVHD) has been controversial in recent mouse and human studies. We carried out studies in a murine acute GVHD model of fully major histocompatibility complex-mismatched myeloablative bone marrow transplantation. We showed that donor wild-type CD4(+) T cells exacerbated acute GVHD compared with IL-17(-/-) CD4(+) T cells, while IL-17 reduced the severity of acute GVHD. The augmentation of acute GVHD by transferred donor IL-17-producing CD4(+) T cells was associated with increased Th1 responses, while IL-17 decreased the percentages of Th1 cells in the GVHD target organs...
October 17, 2016: Cellular & Molecular Immunology
Ariane Roemer, Ulrike Köhl, Omid Majdani, Stephan Klöß, Christine Falk, Sabine Haumann, Thomas Lenarz, Andrej Kral, Athanasia Warnecke
BACKGROUND: The success of cochlear implantation may be further improved by minimizing implantation trauma. The physical trauma of implantation and subsequent immunological sequelae can affect residual hearing and the viability of the spiral ganglion. An ideal electrode should therefore decrease post-implantation trauma and provide support to the residual spiral ganglion population. Combining a flexible electrode with cells producing and releasing protective factors could present a potential means to achieve this...
October 7, 2016: Stem Cell Research & Therapy
Stavroula Masouridi-Levrat, Federico Simonetta, Yves Chalandon
Bone marrow failure (BMF) syndromes are severe complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this paper, we distinguish two different entities, the graft failure (GF) and the poor graft function (PGF), and we review the current understanding of the interactions between the immune and hematopoietic compartments in these conditions. We first discuss how GF occurs as the result of classical alloreactive immune responses mediated by residual host cellular and humoral immunity persisting after conditioning and prevented by host and donor regulatory T cells...
2016: Frontiers in Immunology
Jérémie Martinet, Gwladys Bourdenet, Amine Meliani, Laetitia Jean, Sahil Adriouch, Jose L Cohen, Federico Mingozzi, Olivier Boyer
BACKGROUND: Gene therapy is a promising treatment option for hemophilia and other protein deficiencies. However, immune responses against the transgene product represent an obstacle to safe and effective gene therapy, urging for the implementation of tolerization strategies. Induction of a hematopoietic chimerism via bone marrow transplantation (BMT) is a potent means for inducing immunological tolerance in solid organ transplantation. OBJECTIVES: We reasoned, here, that the same viral vector could be used, first, to transduce BM cells for inducing chimerism-associated transgene-specific immune tolerance and, second, for correcting protein deficiencies by vector-mediated systemic production of the deficient coagulation factor...
2016: Frontiers in Immunology
Laura Carretero-Iglesia, Laurence Bouchet-Delbos, Cédric Louvet, Lucile Drujont, Mercedes Segovia, Emmanuel Merieau, Elise Chiffoleau, Régis Josien, Marcelo Hill, Maria-Cristina Cuturi, Aurélie Moreau
BACKGROUND: Regulatory myeloid cell (RMC) therapy is a promising strategy for the treatment of immunological disorders such as autoimmune disease and allograft transplant rejection. Various RMC subsets can be derived from total bone marrow using different protocols, but their phenotypes often overlap, raising questions about whether they are truly distinct. METHODS: In this study, we directly compared the phenotype and function of 3 types of RMCs, tolerogenic dendritic cells, suppressor macrophages, and myeloid-derived suppressor cells, generated in vitro from the same mouse strain in a single laboratory...
October 2016: Transplantation
Martina Ahlmann, Georg Hempel
Cyclophosphamide is an alkylating agent belonging to the group of oxazaphosporines. As cyclophosphamide is in clinical use for more than 40 years, there is a lot of experience using this drug for the treatment of cancer and as an immunosuppressive agent for the treatment of autoimmune and immune-mediated diseases. Besides antimitotic and antireplicative effects, cyclophosphamide has immunosuppressive as well as immunomodulatory properties. Cyclophosphamide shows selectivity for T cells and is therefore now frequently used in tumour vaccination protocols and to control post-transplant allo-reactivity in haplo-identical unmanipulated bone marrow after transplantation...
October 2016: Cancer Chemotherapy and Pharmacology
Subha Karumuthil-Melethil, Steven J Gray
Globoid cell leukodystrophy (GLD, or Krabbe's disease) is a severe inherited neurodegenerative disease caused by the lack of a lysosomal enzyme, GALC. The disease has been characterized in humans as well as three naturally occurring animal models, murine, canine, and nonhuman primate. Multiple treatment strategies have been explored for GLD, including enzyme replacement therapy, small-molecule pharmacological approaches, gene therapy, and bone marrow transplant. No single therapeutic approach has proved to be entirely effective, and the reason for this is not well understood...
November 2016: Journal of Neuroscience Research
Agnieszka Ciomber, Iwona Mitrus, Wojciech Fidyk, Andrzej Smagur, Agata Chwieduk, Magdalena Glowala-Kosinska, Tomasz Czerw, Małgorzata Sobczyk-Kruszelnicka, Włodzimierz Mendrek, Maria Sadus-Wojciechowska, Jacek Najda, Jerzy Holowiecki, Sebastian Giebel
Regeneration of the bone marrow microenvironment after transplantation of allogeneic hematopoietic stem cells is poorly explored. The goal of our study was to investigate this process focusing on immunologic factors: concentrations of selected cytokines, expression of immunosuppressive proteins CD47 and CD274 on hematopoietic stem cells, and frequency of T regulatory lymphocytes (Tregs). Bone marrow samples were collected before transplantation, on the day of transplantation, and at the 1-year follow-up. As a control group, we used bone marrow from healthy donors...
August 12, 2016: Experimental Hematology
J B Bridges, J K Houston
CBA mice exposed to an otherwise lethal dose of irradiation (1006 rads) were saved by the intravenous injection of suspensions of CBA bone marrow cells. Hamster kidney cells (BHK) were injected intraperitoneally into these mice at 1, 3, 7 and 14 days after irradiation and marrow injection. The injected cells survived and proliferated in the abdominal cavities of the mice. The cells invaded abdominal organs and the skeletal muscle of the body wall. Mice injected with BHK cells 24 hours after irradiation and marrow injection survived 11-23 days...
December 1975: Irish Journal of Medical Science
R Foà, M T Fierro, S Tosti, G Meloni, F Gavosto, F Mandelli
A complete and persistent clinico-hematologic remission was obtained in an M4 acute myeloid leukemia patient after treatment with recombinant interleukin 2 (rIL2) alone. After two autologous bone-marrow transplantations and in the third relapse with 10% persistent blasts in the marrow, the patient was treated with two intensive courses of rIL2 given by continuous infusion over a period of 13 days. rIL2 administration was accompanied by significant side effects and followed by notable hematological, clinical and immunological modifications...
1990: Leukemia & Lymphoma
Geoffrey D E Cuvelier, Tamar S Rubin, Donna A Wall, Marlis L Schroeder
ZAP70 deficiency is a rare T + B + NK+ combined immunodeficiency with limited outcome data to help guide decisions around hematopoietic stem cell transplant (HSCT). We sought to understand the long-term clinical and immunologic outcomes of both conditioned and unconditioned HSCT for ZAP70 deficiency following transplant from a variety of graft sources. We performed a retrospective, single center review of all cases of HSCT for genetically confirmed ZAP70 deficiency since 1992. At a median of 13.5-year post-HSCT, 8/8 (100 %) patients are alive...
October 2016: Journal of Clinical Immunology
Florence Morin, Niloufar Kavian, Carole Nicco, Olivier Cerles, Christiane Chéreau, Frédéric Batteux
Sclerodermatous GVHD (Scl-GVHD), a frequent complication of allogeneic hematopoietic stem cell graft, shares many features with systemic sclerosis, such as production of autoantibodies and fibrosis of skin and inner organs. Recent reports on the implication of STAT3 and of Wnt/β-catenin in fibrosis have prompted us to investigate the effects of the inhibition of both signaling pathways in a mouse model of Scl-GVHD, using niclosamide an anthelmintic drug with well-defined safety profile. Scl-GVHD was induced in BALB/c mice by B10...
July 13, 2016: Journal of Investigative Dermatology
Intan Hakimah Ismail, Faizah Mohamed Jamli, Ida Shahnaz Othman, Lokman Mohd Noh, Amir Hamzah Abdul Latiff
The awareness of primary immunodeficiency (PID) in Malaysia is still not forthcoming. Certain practical issues such as lack of clinical immunologists and specialized laboratory diagnostic facilities remain to be addressed. However, great efforts taken by passionate clinicians and scientists in the immunology networking have ascertained some prevalence. Despite the limitation, all suspected cases of PID are being properly investigated and competently managed. In this case report we highlighted the obstacles we faced in managing PID patients, particularly preparing for bone marrow transplant...
2016: Children
G R Hill, W Krenger, J L Ferrara
Giaft versus host disease (GVHD) remains the principal complication limiting the wider application of allogeneic bone marrow transplantation (BMT). Advances in basic immunology during the last decade have demonstrated how interactions between immunologically competent cells are governed by cytokines, and much recent research has focused on the roles of these mediators in the pathogenesis of acute GVHD. This article will review current evidence that dysregulated cytokine production can be considered a cascade of sequential activation of T-cells and monocytes that is responsible for many of the manifestations of acute GVHD...
1997: Hematology (Amsterdam, Netherlands)
Lucie Leveque-El Mouttie, Motoko Koyama, Laetitia Le Texier, Kate A Markey, Melody Cheong, Rachel D Kuns, Katie E Lineburg, Bianca E Teal, Kylie A Alexander, Andrew D Clouston, Bruce R Blazar, Geoffrey R Hill, Kelli P A MacDonald
Chronic graft-versus-host disease (cGVHD) is a major cause of late mortality following allogeneic bone marrow transplantation (BMT) and is characterized by tissue fibrosis manifesting as scleroderma and bronchiolitis obliterans. The development of acute GVHD (aGVHD) is a powerful clinical predictor of subsequent cGVHD, suggesting that aGVHD may invoke the immunologic pathways responsible for cGVHD. In preclinical models in which sclerodermatous cGVHD develops after a preceding period of mild aGVHD, we show that antigen presentation within major histocompatibility complex (MHC) class II of donor dendritic cells (DCs) is markedly impaired early after BMT...
August 11, 2016: Blood
Ulrike Baranyi, Andreas M Farkas, Karin Hock, Benedikt Mahr, Birgit Linhart, Martina Gattringer, Margit Focke-Tejkl, Arnd Petersen, Fritz Wrba, Thomas Rülicke, Rudolf Valenta, Thomas Wekerle
BACKGROUND: Therapeutic strategies for the prophylaxis of IgE-mediated allergy remain an unmet medical need. Cell therapy is an emerging approach with high potential for preventing and treating immunological diseases. We aimed to develop a cell-based therapy inducing permanent allergen-specific immunological tolerance for preventing IgE-mediated allergy. METHODS: Wild-type mice were treated with allergen-expressing bone marrow cells under a short course of tolerogenic immunosuppression (mTOR inhibition and costimulation blockade)...
May 2016: EBioMedicine
Crystal Dykstra, Amanda J Lee, Evan J Lusty, Mira M Shenouda, Mahsa Shafai, Fatemeh Vahedi, Marianne V Chew, Stephen Collins, Ali A Ashkar
BACKGROUND: Humanized mouse models are an increasingly popular preclinical model to study the human immune response in a biological system. There are a variety of protocols to generate these mice, each differing in the strain of the recipient, source of hematopoietic stem cells, and mode of transplantation. Though there is well-documented reconstitution information regarding the spleen, blood, and bone marrow, there is little information regarding reconstitution of the lymph node and liver...
2016: BMC Immunology
Vaclava Polivkova, Peter Rohon, Hana Klamova, Olga Cerna, Martina Divoka, Nikola Curik, Jan Zach, Martin Novak, Iuri Marinov, Simona Soverini, Edgar Faber, Katerina Machova Polakova
Bone marrow transplantation or ponatinib treatment are currently recommended strategies for management of patients with chronic myeloid leukemia (CML) harboring the T315I mutation and compound or polyclonal mutations. However, in some individual cases, these treatment scenarios cannot be applied. We used an alternative treatment strategy with interferon-α (IFN-α) given solo, sequentially or together with TKI in a group of 6 cases of high risk CML patients, assuming that the TKI-independent mechanism of action may lead to mutant clone repression...
2016: PloS One
Eduardo Esteban-Zubero, Francisco Agustín García-Gil, Laura López-Pingarrón, Moisés Alejandro Alatorre-Jiménez, Pablo Iñigo-Gil, Dun-Xian Tan, José Joaquín García, Russel J Reiter
Organ transplantation is a useful therapeutic tool for patients with end-stage organ failure; however, graft rejection is a major obstacle in terms of a successful treatment. Rejection is usually a consequence of a complex immunological and nonimmunological antigen-independent cascade of events, including free radical-mediated ischemia-reperfusion injury (IRI). To reduce the frequency of this outcome, continuing improvements in the efficacy of antirejection drugs are a top priority to enhance the long-term survival of transplant recipients...
June 2016: Journal of Endocrinology
Martin Szyska, Il-Kang Na
The bone marrow is the origin of all hematopoietic lineages and an important homing site for memory cells of the adaptive immune system. It has recently emerged as a graft-versus-host disease (GvHD) target organ after allogeneic stem cell transplantation (alloHSCT), marked by depletion of both hematopoietic progenitors and niche-forming cells. Serious effects on the restoration of hematopoietic function and immunological memory are common, especially in patients after myeloablative conditioning therapy. Cytopenia and durable immunodeficiency caused by the depletion of hematopoietic progenitors and destruction of bone marrow niches negatively influence the outcome of alloHSCT...
2016: Frontiers in Immunology
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