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https://www.readbyqxmd.com/read/28099485/cell-based-systems-biology-analysis-of-human-as03-adjuvanted-h5n1-avian-influenza-vaccine-responses-a-phase-i-randomized-controlled-trial
#1
Leigh M Howard, Kristen L Hoek, Johannes B Goll, Parimal Samir, Allison Galassie, Tara M Allos, Xinnan Niu, Laura E Gordy, C Buddy Creech, Nripesh Prasad, Travis L Jensen, Heather Hill, Shawn E Levy, Sebastian Joyce, Andrew J Link, Kathryn M Edwards
BACKGROUND: Vaccine development for influenza A/H5N1 is an important public health priority, but H5N1 vaccines are less immunogenic than seasonal influenza vaccines. Adjuvant System 03 (AS03) markedly enhances immune responses to H5N1 vaccine antigens, but the underlying molecular mechanisms are incompletely understood. OBJECTIVE AND METHODS: We compared the safety (primary endpoint), immunogenicity (secondary), gene expression (tertiary) and cytokine responses (exploratory) between AS03-adjuvanted and unadjuvanted inactivated split-virus H5N1 influenza vaccines...
2017: PloS One
https://www.readbyqxmd.com/read/28097812/monitoring-immune-response-after-allogeneic-transplantation-of-mesenchymal-stem-cells-for-osteochondral-repair
#2
Elhussein Elbadry Mahmoud, Tanaka Yuka, Naosuke Kamei, Yohei Harada, Hideki Ohdan, Adachi Nobuo, Mitsuo Ochi
The aim of this study was to investigate safety of using allogeneic magnetically labeled mesenchymal stem cells (m-MSCs) to ameliorate osteochondral repair as well as autologous one, with immune surveillance using a mixed lymphocyte reaction (MLR) assay. Twenty knees of Japanese white rabbits were randomly divided into two groups: the control (autologous) group, the transplantation of 2 × 10(5)  m-MSCs and the experimental (allogeneic) group, transplantation of 2 × 10(5)  m-MSCs from Dutch rabbit was performed, with exposure to an external magnetic device for 10 minutes, then rabbits were euthanized after 12 weeks...
January 17, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28096093/lymphangiogenesis-is-a-feature-of-acute-gvhd-and-vegfr-3-inhibition-protects-against-experimental-gvhd
#3
Sarah Mertlitz, Yu Shi, Martina Kalupa, Carsten Grötzinger, Jörg Mengwasser, Katarina Riesner, Steffen Cordes, Sefer Elezkurtaj, Olaf Penack
Lymph vessels play a crucial role for immune reactions in health and disease. In oncology the inhibition of lymphangiogenesis is an established therapeutic concept to reduce metastatic spreading of tumor cells. During allogeneic tissue transplantation the inhibition of lymphangiogenesis has been successfully used to attenuate graft rejection. Despite its critical importance for tumor growth, allo-immune responses and inflammation, the role of lymphangiogenesis has not been investigated during allogeneic hematopoietic stem cell transplantation (allo-HSCT)...
January 17, 2017: Blood
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
#4
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/28090089/transfer-of-minimally-manipulated-cmv-specific-t-cells-from-stem-cell-or-third-party-donors-to-treat-cmv-infection-after-allohsct
#5
M Neuenhahn, J Albrecht, M Odendahl, F Schlott, G Dössinger, M Schiemann, S Lakshmipathi, K Martin, D Bunjes, S Harsdorf, E M Weissinger, H Menzel, M Verbeek, L Uharek, N Kröger, E Wagner, G Kobbe, T Schroeder, M Schmitt, G Held, W Herr, L Germeroth, H Bonig, T Tonn, H Einsele, D H Busch, G U Grigoleit
Cytomegalovirus (CMV) infection is a common, potentially life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). We assessed prospectively safety and efficacy of stem cell-donor- or third-party-donor-derived CMV-specific T cells for the treatment of persistent CMV infections after allo-HSCT in a phase I/IIa trial. Allo-HSCT patients with drug-refractory CMV infection and lacking virus-specific T cells were treated with a single dose of ex vivo MHC-Streptamer-isolated CMV epitope-specific donor T cells...
January 16, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28088653/immune-stimulation-during-chemotherapy-increases-incidence-of-acute-graft-versus-host-disease-in-acute-myeloid-leukemia-a-study-on-behalf-of-sfgm-tc-and-alfa
#6
Lining Wang, Emmanuel Raffoux, Xavier Thomas, Ibrahim Yakoub-Agha, Jean-Henri Bouhris, Stéphane de Botton, Mauricette Michallet, Stéphanie Nguyen Quoc, Xavier Troussard, Eric Deconinck, Denis Caillot, Pascal Turlure, Stéphane Vigouroux, Arnaud Pigneux, Anne Huynh, Jean-Valère Malfuson, Michael Loschi, Gerard Socie, Hervé Dombret, Régis Peffault de la Tour, Thomas Cluzeau
60-70% of AML patients have an indication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) during their treatment. Graft versus host disease (GvHD), the major cause of mortality and comorbidities post-transplantation, develops by immunological mechanism and decides greatly prognosis and quality of life (QoL) of graft recipient. Current GvHD prophylaxis is not personalized. Infections, toxicities and leukemic infiltration complicate the first chemotherapy phases prior to allo-HSCT. They, to certain extent, induce local immune stimulation...
January 5, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28073320/early-recovery-of-t-cell-function-predicts-improved-survival-after-t-cell-depleted-allogeneic-transplant
#7
Jenna D Goldberg, Junting Zheng, Ravin Ratan, Trudy N Small, Kuan-Chi Lai, Farid Boulad, Hugo Castro-Malaspina, Sergio A Giralt, Ann A Jakubowski, Nancy A Kernan, Richard J O'Reilly, Esperanza B Papadopoulos, James W Young, Marcel R M van den Brink, Glenn Heller, Miguel-Angel Perales
Infection, relapse, and GVHD can complicate allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although the effect of poor immune recovery on infection risk is well-established, there are limited data on the effect of immune reconstitution on relapse and survival, especially following T-cell depletion (TCD). To characterize the pattern of immune reconstitution in the first year after transplant and its effects on survival and relapse, we performed a retrospective study in 375 recipients of a myeloablative TCD allo-HSCT for hematologic malignancies...
January 10, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28057639/clinical-and-immunologic-impact-of-ccr5-blockade-in-graft-versus-host-disease-prophylaxis
#8
Ryan H Moy, Austin P Huffman, Lee P Richman, Lisa Crisalli, Ximi K Wang, James A Hoxie, Rosemarie Mick, Stephen G Emerson, Yi Zhang, Robert H Vonderheide, David L Porter, Ran Reshef
Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Lymphocyte trafficking via chemokine receptors such as CCR5 plays a critical role in alloreactive responses, and previous data suggest that CCR5 blockade with maraviroc results in a low incidence of visceral GVHD. However, the full scope of clinical and immunologic effects of CCR5 blockade in HSCT has not been described. We compared a cohort of patients enrolled on a trial of reduced-intensity allo-HSCT with standard GVHD prophylaxis plus maraviroc to a contemporary control cohort receiving standard GVHD prophylaxis alone...
January 5, 2017: Blood
https://www.readbyqxmd.com/read/28049555/foxp3-positive-regulatory-t-cells-and-kidney-allograft%C3%A2-tolerance
#9
REVIEW
Alessandro Alessandrini, Laurence A Turka
Normal immune homeostasis is achieved by several mechanisms, and prominent among them is immunoregulation. Although several types of regulatory lymphocyte populations have been described, CD4 T cells expressing the FOXP3 transcription factor (FOXP3-positive regulatory T cells [FOXP3(+) Tregs]) are the best understood. This population of cells is critical for maintaining self-tolerance throughout the life of the organism. FOXP3(+) Tregs can develop within the thymus, but also under select circumstances, naive peripheral T cells can be induced to express FOXP3 and become stable Tregs as well...
December 31, 2016: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/28028710/restoring-ovarian-endocrine-function-with-encapsulated-ovarian-allograft-in-immune-competent-mice
#10
Anu David, James Ronald Day, Alexa Leigh Cichon, Adam Lefferts, Marilia Cascalho, Ariella Shikanov
Premature ovarian insufficiency (POI) is a major complication of cytotoxic treatments due to extreme ovarian sensitivity to chemotherapy and radiation. In pediatric cancer patients modern therapy has improved the long-term survival to over 80% in the United States. However, these cancer survivors face long-term health problems related to treatment toxicity. In female cancer survivors POI leads to sterility, along with the consequences of estrogen deficiency such as premature osteopenia, muscle wasting, accelerated cardiovascular diseases and a vast array of other health and developmental problems...
December 27, 2016: Annals of Biomedical Engineering
https://www.readbyqxmd.com/read/28024499/-clinical-efficacy-of-haploidentical-allo-hsct-of-reduced-intensity-preconditioning-combined-with-induced-immune-tolerance-after-transplantation-for-severe-aplastic-anemia
#11
Zhi Guo, Hui-Ren Chen, Xiao-Dong Liu, Kai Yang, Jing-Xing Lou, Yuan Zhang, Peng Chen, Xue-Peng He
OBJECTIVE: To investigate the efficacy and safety of haploidentical allo-HSCT in combination of reduced intensity preconditioning combined with cyclophosphamid (CTX)-induced immune tolerance after transplanitation for treatment of severe aplastic anemia (SAA). METHODS: A total of 15 patients with SAA received the haploidentical allo-HSCT of reduced intensity preconditioning combined with CTX-induced immune tolerance after transplartation in the General hospital of Beijing military command of chinese PLA from June 2012 to December 2014...
December 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/27989895/intraperitoneal-injection-of-ido-expressing-dermal-fibroblasts-improves-the-allograft-survival
#12
Mohsen Khosravi-Maharlooei, MohammadReza Pakyari, Reza B Jalili, Ruhangiz T Kilani, Aziz Ghahary
Indoleamine 2,3-dioxygenase (IDO) is an immunosuppressive enzyme with tolerogenic effects on different immune cells. Our group has previously shown that co-transplantation of IDO-expressing fibroblasts with donor tissues can delay immune rejection by inducing local immunosuppression. In this study, we have employed a systemic approach to improve allograft survival without using any immunosuppressive medication. To achieve this, 10 million lentiviral transduced IDO-expressing donor derived fibroblasts were injected into the peritoneal cavity of allograft recipients...
October 29, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27965674/molecular-and-cellular-characterization-of-human-cd8-t-suppressor-cells
#13
REVIEW
Zheng Xu, Sophey Ho, Chih-Chao Chang, Qing-Yin Zhang, Elena-Rodica Vasilescu, George Vlad, Nicole Suciu-Foca
Bidirectional interactions between dendritic cells and Ag-experienced T cells initiate either a tolerogenic or immunogenic pathway. The outcome of these interactions is of crucial importance in malignancy, transplantation, and autoimmune diseases. Blockade of costimulation results in the induction of T helper cell anergy and subsequent differentiation of antigen-specific CD8(+) T suppressor/regulatory cells (Ts). Ts, primed in the presence of inhibitory signals, exert their inhibitory function in an antigen-specific manner, a feature with tremendous clinical potential...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27943117/serum-igm-levels-independently-predict-immune-response-to-influenza-vaccine-in-long-term-survivors-vaccinated-at-1%C3%A2-year-after-undergoing-allogeneic-hematopoietic-stem-cell-transplantation
#14
Yusuke Fukatsu, Yasuyuki Nagata, Miwa Adachi, Tomohiro Yagyu, Takaaki Ono
Influenza virus infection can cause fatal complications (e.g., pneumonia) in immunodeficient long-term survivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The immune response to the vaccine improves if it is administered at >1 year after allo-HSCT, although the response may vary according to the patient's immune status. We sought to identify predictors of immune response to trivalent inactivated influenza vaccine (TIV) among patients vaccinated at >1 year after allo-HSCT. We included 27 allo-HSCT recipients, with a median interval of 4...
December 10, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27940475/the-intestinal-microbiota-in-allogeneic-hematopoietic-cell-transplant-and-graft-versus-host-disease
#15
Anna Staffas, Marina Burgos da Silva, Marcel R M van den Brink
Hematopoietic cell transplantation (HCT) is a critical treatment for patients with high-risk hematopoietic malignancies, hematological deficiencies, and other immune diseases. In allogeneic HCT (allo-HCT), donor derived T cells recognize host tissues as foreign causing graft-versus-host disease (GvHD) which is a main contributor to morbidity and mortality. The intestine is one of the organs most severely affected by GvHD and research has recently highlighted the importance of bacteria, particularly the gut microbiota, in HCT outcome and in GvHD development...
December 9, 2016: Blood
https://www.readbyqxmd.com/read/27939210/studies-of-innate-immune-systems-against-human-cells
#16
Rieko Sakai, Etsuko Kitano, Akira Maeda, Pei-Chi Lo, Hiroshi Eguchi, Masahito Watanabe, Hiroshi Nagashima, Hiroomi Okuyama, Shuji Miyagawa
BACKGROUND: Pigs are frequently used as animal models for experiments in the surgical field, including allo- and xeno-transplantation. Regeneration studies, including studies dealing with human- and monkey-induced pluripotent stem cells (iPSC), have gradually progressed, with pigs sometimes being used as the scaffold. However, the immunological response of pigs against humans, especially innate immunities, remain unclear. This study reports on a comprehensive study of pig innate immunity against humans...
December 7, 2016: Transplant Immunology
https://www.readbyqxmd.com/read/27927647/gvhd-prevents-nk-cell-dependent-leukemia-and-virus-specific-innate-immunity
#17
Mark D Bunting, Antiopi Varelias, Fernando Souza-Fonseca-Guimaraes, Iona S Schuster, Katie E Lineburg, Rachel D Kuns, Peter Fleming, Kelly R Locke, Nicholas D Huntington, Bruce R Blazar, Steven W Lane, Siok-Keen Tey, Kelli P A MacDonald, Mark J Smyth, Mariapia A Degli-Esposti, Geoffrey R Hill
Allogeneic bone marrow transplantation (allo-BMT) is a curative therapy for hematological malignancies, but is associated with significant complications, principally graft-versus-host disease (GVHD) and opportunistic infections. Natural killer (NK) cells mediate important innate immunity that provides a temporal bridge until the reconstruction of adaptive immunity. Here we show that the development of GVHD after allo-BMT prevented NK-cell reconstitution, particularly within the maturing M1 and M2 NK-cell subsets in association with exaggerated activation, apoptosis and autophagy...
December 7, 2016: Blood
https://www.readbyqxmd.com/read/27914923/alloantigen-gene-transfer-to-hepatocytes-promotes-tolerance-to-pancreatic-islet-graft-by-inducing-cd8-regulatory-t-cells
#18
Valentin Le Guen, Jean-Paul Judor, Françoise Boeffard, Vanessa Gauttier, Nicolas Ferry, Jean-Paul Soulillou, Sophie Brouard, Sophie Conchon
BACKGROUND & AIM: Induction of donor-specific immune tolerance is a good alternative to chronic life-long immunosuppression for transplant patients. Donor major histocompatibility complex (MHC) molecules represent the main targets of the allogeneic immune response of transplant recipients. Liver-targeted gene transfer with viral vectors induces tolerance toward the encoded antigen. The aim of this work was to determine whether alloantigen gene transfer to hepatocytes induces tolerance and promotes graft acceptance...
November 30, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27910184/clinical-significance-of-pre-transplant-circulating-cd3-cd4-cd161-cell-frequency-on-the-occurrence-of-neutropenic-infections-after-allogeneic-stem-cell-transplantation
#19
Tae Woo Kim, Sung-Eun Lee, Ji-Young Lim, Da-Bin Ryu, Young-Woo Jeon, Jae-Ho Yoon, Byung-Sik Cho, Ki-Seong Eom, Yoo-Jin Kim, Hee-Je Kim, Seok Lee, Seok-Goo Cho, Dong-Wook Kim, Jong Wook Lee, Woo-Sung Min, Chang-Ki Min
BACKGROUND: Few studies have been performed to identify factors that are associated with an increased risk of infections during the neutropenic period in patients undergoing allogeneic stem cell transplantation (allo-SCT). The aim of this study was to identify the host immune cells responsible for infections before engraftment. METHODS: A total of 282 patients who underwent allo-SCT were enrolled. Peripheral blood samples were collected before conditioning therapy...
December 2, 2016: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/27896368/targeting-of-the-wt191-138-fragment-to-human-dendritic-cells-improves-leukemia-specific-t-cell-responses-providing-an-alternative-approach-to-wt1-based-vaccination
#20
Nergui Dagvadorj, Anne Deuretzbacher, Daniela Weisenberger, Elke Baumeister, Johannes Trebing, Isabell Lang, Carolin Köchel, Markus Kapp, Kerstin Kapp, Andreas Beilhack, Thomas Hünig, Hermann Einsele, Harald Wajant, Götz Ulrich Grigoleit
Due to its immunogenicity and overexpression concomitant with leukemia progression, Wilms tumor protein 1 (WT1) is of particular interest for immunotherapy of AML relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). So far, WT1-specific T-cell responses have mainly been induced by vaccination with peptides presented by certain HLA alleles. However, this approach is still not widely applicable in clinical practice due to common limitations of HLA restriction. Dendritic cell (DC) vaccines electroporated with mRNA encoding full-length protein have also been tested for generating WT1-derived peptides for presentation to T-cells...
November 28, 2016: Cancer Immunology, Immunotherapy: CII
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