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https://www.readbyqxmd.com/read/29781812/pim-2-protein-kinase-negatively-regulates-t-cell-responses-in-transplantation-and-tumor-immunity
#1
Anusara Daenthanasanmak, Yongxia Wu, Supinya Iamsawat, Hung D Nguyen, David Bastian, MengMeng Zhang, M Hanief Sofi, Shilpak Chatterjee, Elizabeth G Hill, Shikhar Mehrotra, Andrew S Kraft, Xue-Zhong Yu
PIM kinase family members play a crucial role in promoting cell survival and proliferation via phosphorylation of their target substrates. In this study, we investigated the role of the PIM kinases with respect to T cell responses in transplantation and tumor immunity. We found that the PIM-2 isoform negatively regulated T cell responses to alloantigen, in contrast to the PIM-1 and PIM-3 isoforms, which acted as positive regulators. T cells deficient in PIM-2 demonstrated increased T cell differentiation toward Th1 subset, proliferation, and migration to target organs after allogeneic bone marrow transplantation, resulting in dramatically accelerated graft-versus-host disease (GVHD) severity...
May 21, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29773597/hematopoietic-stem-cell-loss-and-hematopoietic-failure-in-severe-aplastic-anemia-is-driven-by-macrophages-and-aberrant-podoplanin-expression
#2
Amanda McCabe, Julianne N P Smith, Angelica Costello, Jackson Maloney, Divya Katikaneni, Katherine C MacNamara
Severe aplastic anemia results from profound hematopoietic stem cell loss. T cells and interferon gamma have long been associated with severe aplastic anemia, yet the underlying mechanisms driving hematopoietic stem cell loss remain unknown. Using a mouse model of severe aplastic anemia, we demonstrate that interferon gamma-dependent hematopoietic stem cell loss required macrophages. Interferon gamma was necessary for bone marrow macrophage persistence, despite loss of other myeloid cells and hematopoietic stem cells...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29773281/-cutaneous-and-systemic-t-cell-lymphoma-treated-with-haploidentical-bone-marrow-transplantation
#3
M Méchineaud, M Mercier, Y Le Corre, A Croué, N Ifrah, L Martin
BACKGROUND: Herein, we report a case of systemic cutaneous T-cell lymphoma refractory to standard therapy, the course of which resulted in haplo-identical bone marrow grafting. PATIENTS AND METHODS: A 53-year-old woman consulted for facial erythema with infiltration, keratotic lesions on the trunk, and adenopathies measuring around 1cm on the axilla and inguinal folds. A diagnosis was made of Sézary syndrome (SS), a leukaemic form of epidermotropic cutaneous T-cell lymphoma...
May 14, 2018: Annales de Dermatologie et de Vénéréologie
https://www.readbyqxmd.com/read/29769782/graft-versus-host-disease-presenting-as-fibrosing-alopecia-in-a-pattern-distribution-a-model-for-pathophysiological-understanding-of-cicatricial-pattern-hair-loss
#4
Hudson Dutra Rezende, Maria Fernanda Reis Gavazzoni Dias, Ralph Michel Trüeb
A case of cutaneous graft versus host disease (GvHD) presenting as fibrosing alopecia in a pattern distribution (FAPD) is discussed, possibly providing a mechanistic model for a better understanding of the pathogenic events underlying cicatricial pattern hair loss. The implication of a follicular inflammation and fibrosis associated with patterned hair loss has emerged from several independent studies. Eventually, Zinkernagel and Trüeb reported a peculiar type of cicatricial pattern hair loss with histopathological features consistent with lichen planopilaris (LPP) associated with androgenetic alopecia (AGA)...
March 2018: International Journal of Trichology
https://www.readbyqxmd.com/read/29769264/rhoa-g17v-is-sufficient-to-induce-autoimmunity-and-promotes-t-cell-lymphomagenesis-in-mice
#5
Samuel Y Ng, Leon Brown, Kristen Stevenson, Tiffany deSouza, Jon C Aster, Abner Louissaint, David M Weinstock
Patients with angioimmunoblastic T-cell lymphoma (AITL) and other peripheral T-cell lymphomas (PTCL) that harbor features of follicular helper T (TFH) cells have a very poor prognosis. These lymphomas commonly present with paraneoplastic autoimmunity and lymphopenia. RhoA G17V mutation is present in 60% of TFH-like lymphomas but its role in tumorigenesis is poorly understood. We generated transgenic mice that express RhoA G17V under the control of murine CD4 regulatory elements at levels comparable to a heterozygous mutation (tgRhoA mice)...
May 16, 2018: Blood
https://www.readbyqxmd.com/read/29762163/transcriptional-gene-silencing-limits-cxcr4-associated-depletion-of-bone-marrow-cd34-cells-in-hiv-1-infection
#6
Tetsuo Tsukamoto
OBJECTIVES: Hematological abnormalities that include changes in bone marrow, such as in anemia and pancytopenia, are common among human immunodeficiency virus (HIV)-infected patients, particularly in the advanced stage of disease. Such abnormalities may be caused by a reduced bone marrow function for hematopoiesis. This aim of this study was to determine whether transcriptional gene silence can help to preserve the hosts' hematopoietic potential in addition to peripheral CD4 T cells against CCR5-tropic HIV infection...
May 11, 2018: AIDS
https://www.readbyqxmd.com/read/29761169/prolonged-cenicriviroc-therapy-reduces-hepatic-fibrosis-despite-steatohepatitis-in-a-diet-induced-mouse-model-of-nonalcoholic-steatohepatitis
#7
Annie J Kruger, Bryan C Fuchs, Ricard Masia, Jacinta A Holmes, Shadi Salloum, Mozhdeh Sojoodi, Diego S Ferreira, Stephanie M Rutledge, Peter Caravan, Nadia Alatrakchi, Pam Vig, Eric Lefebvre, Raymond T Chung
Nonalcoholic steatohepatitis (NASH) is a progressive liver disease projected to become the leading cause of cirrhosis and liver transplantation in the next decade. Cenicriviroc (CVC), a dual chemokine receptor 2 and 5 antagonist, prevents macrophage trafficking and is under clinical investigation for the treatment of human NASH fibrosis. We assessed the efficacy and durability of short and prolonged CVC therapy in a diet-induced mouse model of NASH, the choline deficient, L-amino acid-defined, high-fat diet (CDAHFD) model...
May 2018: Hepatology communications
https://www.readbyqxmd.com/read/29755367/the-transcription-factor-hif-1-enhances-the-radio-resistance-of-mouse-mscs
#8
Irene Calvo-Asensio, Eugène T Dillon, Noel F Lowndes, Rhodri Ceredig
Mesenchymal stromal cells (MSCs) are multipotent progenitors supporting bone marrow hematopoiesis. MSCs have an efficient DNA damage response (DDR) and are consequently relatively radio-resistant cells. Therefore, MSCs are key to hematopoietic reconstitution following total body irradiation (TBI) and bone marrow transplantation (BMT). The bone marrow niche is hypoxic and via the heterodimeric transcription factor Hypoxia-inducible factor-1 (Hif-1), hypoxia enhances the DDR. Using gene knock-down, we have previously shown that the Hif-1α subunit of Hif-1 is involved in mouse MSC radio-resistance, however its exact mechanism of action remains unknown...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29754170/cardiac-support-device-asd-delivers-bone-marrow-stem-cells-repetitively-to-epicardium-has-promising-curative-effects-in-advanced-heart-failure
#9
Shizhong Yue, Muhammad Naveed, Wang Gang, Dingding Chen, Zhijie Wang, Feng Yu, Xiaohui Zhou
Ventricular restraint therapy is a non-transplant surgical option for the management of advanced heart failure (HF). To augment the therapeutic applications, it is hypothesized that ASD shows remarkable capabilities not only in delivering stem cells but also in dilated ventricles. Male SD rats were divided into four groups (n = 6): normal, HF, HF + ASD, and HF + ASD-BMSCs respectively. HF was developed by left anterior descending (LAD) coronary artery ligation in all groups except normal group. Post-infarcted electrocardiography (ECG) and brain natriuretic peptide (BNP) showed abnormal heart function in all model groups and HF + ASD-BMSCs group showed significant improvement as compared to other HF, HF + ASD groups on day 30...
May 12, 2018: Biomedical Microdevices
https://www.readbyqxmd.com/read/29752065/cd36-mediates-cell-surface-antigens-to-promote-thymic-development-of-the-regulatory-t-cell-receptor-repertoire-and-allo-tolerance
#10
Justin S A Perry, Emilie V Russler-Germain, You W Zhou, Whitney Purtha, Matthew L Cooper, Jaebok Choi, Mark A Schroeder, Vanessa Salazar, Takeshi Egawa, Byeong-Chel Lee, Nada A Abumrad, Brian S Kim, Mark S Anderson, John F DiPersio, Chyi-Song Hsieh
The development of T cell tolerance in the thymus requires the presentation of host proteins by multiple antigen-presenting cell (APC) types. However, the importance of transferring host antigens from transcription factor AIRE-dependent medullary thymic epithelial cells (mTECs) to bone marrow (BM) APCs is unknown. We report that antigen was primarily transferred from mTECs to CD8α+ dendritic cells (DCs) and showed that CD36, a scavenger receptor selectively expressed on CD8α+ DCs, mediated the transfer of cell-surface, but not cytoplasmic, antigens...
April 30, 2018: Immunity
https://www.readbyqxmd.com/read/29748647/isolation-and-functional-assessment-of-mouse-skeletal-stem-cell-lineage
#11
Gunsagar S Gulati, Matthew P Murphy, Owen Marecic, Michael Lopez, Rachel E Brewer, Lauren S Koepke, Anoop Manjunath, Ryan C Ransom, Ankit Salhotra, Irving L Weissman, Michael T Longaker, Charles K F Chan
There are limited methods available to study skeletal stem, progenitor, and progeny cell activity in normal and diseased contexts. Most protocols for skeletal stem cell isolation are based on the extent to which cells adhere to plastic or whether they express a limited repertoire of surface markers. Here, we describe a flow cytometry-based approach that does not require in vitro selection and that uses eight surface markers to distinguish and isolate mouse skeletal stem cells (mSSCs); bone, cartilage, and stromal progenitors (mBCSPs); and five downstream differentiated subtypes, including chondroprogenitors, two types of osteoprogenitors, and two types of hematopoiesis-supportive stroma...
June 2018: Nature Protocols
https://www.readbyqxmd.com/read/29743364/t-cell-derived-lymphotoxin-is-essential-for-anti-hsv-1-humoral-immune-response
#12
Kaiting Yang, Yong Liang, Zhichen Sun, Diyuan Xue, Hairong Xu, Mingzhao Zhu, Yang-Xin Fu, Hua Peng
B cell-derived lymphotoxin (LT) is required for the development of follicular dendritic cell clusters for the formation of primary and secondary lymphoid follicles, but the role of T cell-derived LT in antibody response has not been well demonstrated. We observed that lymphotoxin-β-receptor (LTβR) signaling is essential for optimal humoral immune response and protection against an acute HSV-1 infection. Blocking the LTβR pathway caused poor maintenance of germinal center B (GC-B) cells and follicular helper T (Tfh) cells...
May 9, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29740442/stability-of-chimerism-in-non-obese-diabetic-mice-achieved-by-rapid-t-cell-depletion-is-associated-with-high-levels-of-donor-cells-very-early-after-transplant
#13
Jiaxin Lin, William F N Chan, Louis Boon, Colin C Anderson
Stable mixed hematopoietic chimerism is a robust method for inducing donor-specific tolerance with the potential to prevent rejection of donor islets in recipients with autoimmune type-1 diabetes. However, with reduced intensity conditioning, fully allogeneic chimerism in a tolerance resistant autoimmune-prone non-obese diabetic (NOD) recipient has rarely been successful. In this setting, successful multilineage chimerism has required either partial major histocompatability complex matching, mega doses of bone marrow, or conditioning approaches that are not currently clinically feasible...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29740426/multipotent-adult-progenitor-cells-suppress-t-cell-activation-in-in-vivo-models-of-homeostatic-proliferation-in-a-prostaglandin-e2-dependent-manner
#14
Fiona Carty, Jennifer M Corbett, João Paulo M C M Cunha, James L Reading, Timothy I M Tree, Anthony E Ting, Samantha R Stubblefield, Karen English
Lymphodepletion strategies are used in the setting of transplantation (including bone marrow, hematopoietic cell, and solid organ) to create space or to prevent allograft rejection and graft versus host disease. Following lymphodepletion, there is an excess of IL-7 available, and T cells that escape depletion respond to this cytokine undergoing accelerated proliferation. Moreover, this environment promotes the skew of T cells to a Th1 pro-inflammatory phenotype. Existing immunosuppressive regimens fail to control this homeostatic proliferative (HP) response, and thus the development of strategies to successfully control HP while sparing T cell reconstitution (providing a functioning immune system) represents a significant unmet need in patients requiring lymphodepletion...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29736095/repair-of-critical-sized-rat-calvarial-defects-with-three-dimensional-hydroxyapatite-gelatin-scaffolds-and-bone-marrow-stromal-stem-cells
#15
Hatef Ghasemi Hamidabadi, Majid Malekzadeh Shafaroudi, Morteza Seifi, Maryam Nazm Bojnordi, Masume Behruzi, Mazaher Gholipourmalekabadi, Ali Malekzadeh Shafaroudi, Nourollah Rezaei
Introduction: The repair of critical-sized defects (CSDs) are one of the most challenging orthopedic problems and the attempts for development of an ideal scaffold for treatment of large bone defect are ongoing. Aim: The aim of this study was the effectiveness of hydroxyapatite-gelatin seeded with bone marrow stromal cells construct for healing of critical-sized bone defect in vivo. Material and Methods: In this experimental study, the bone marrow stromal cells (BMSCs) were isolated by flushing method...
April 2018: Medical Archives
https://www.readbyqxmd.com/read/29707600/preclinical-development-of-a-lentiviral-vector-for-gene-therapy-of-x-linked-severe-combined-immunodeficiency
#16
Valentina Poletti, Sabine Charrier, Guillaume Corre, Bernard Gjata, Alban Vignaud, Fang Zhang, Michael Rothe, Axel Schambach, H Bobby Gaspar, Adrian J Thrasher, Fulvio Mavilio
X-linked severe combined immunodeficiency (SCID-X1) is caused by mutations in the interleukin-2 receptor γ chain gene (IL2RG), and it is characterized by profound defects in T, B, and natural killer (NK) cell functions. Transplantation of hematopoietic stem/progenitor cells (HSPCs) genetically corrected with early murine leukemia retrovirus (MLV)-derived gammaretroviral vectors showed restoration of T cell immunity in patients, but it resulted in vector-induced insertional oncogenesis. We developed a self-inactivating (SIN) lentiviral vector carrying a codon-optimized human IL2RG cDNA driven by the EF1α short promoter (EFS-IL2RG), and we tested its efficacy and safety in vivo by transplanting transduced Il2rg-deficient Lin- HSPCs in an Il2rg -/- / Rag2 -/- mouse model...
June 15, 2018: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/29702747/allogeneic-chondrogenically-differentiated-human-bone-marrow-stromal-cells-do-not-induce-dendritic-cell-maturation
#17
C H Kiernan, A KleinJan, M Peeters, E B Wolvius, E Farrell, P A J Brama
Bone marrow stromal cell (BMSC) mediated endochondral bone formation may be a promising alternative to the current gold standards of autologous bone transplantation, in the development of novel methods for bone repair. Implantation of chondrogenically differentiated BMSCs leads to bone formation in vivo via endochondral ossification. The success of this bone formation in an allogeneic system depends upon the interaction between the implanted constructs and the host immune system. The current study investigated the effect of chondrogenically differentiated hBMSC pellets on the maturation and function of dendritic cells (DCs) by directly co-culturing bone forming chondrogenic hBMSC pellets and immature or lipopolysaccharide (LPS)-matured DCs in vitro...
April 27, 2018: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/29699851/blockade-of-adhesion-molecule-lymphocyte-function-associated-antigen-1-improves-long-term-heart-allograft-survival-in-mixed-chimeras
#18
Nina Pilat, Philipp Sabler, Christoph Klaus, Benedikt Mahr, Lukas Unger, Karin Hock, Mario Wiletel, Christoph Schwarz, Ivan Kristo, Heinz Regele, Thomas Wekerle
BACKGROUND: The mixed chimerism approach for intentional induction of donor-specific tolerance was shown to be successful in various models from mice to humans. For transplant patients, the approach would obviate the need for long-term immunosuppression and associated side effects; moreover, it would preclude the risk of late graft loss due to chronic rejection. Widespread clinical application is hindered by toxicities related to recipient pre-conditioning. Herein we aimed to investigate a clinically relevant protocol for tolerance induction to cardiac allografts, sparing CD40 blockade or T-cell depletion...
March 30, 2018: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/29685843/clinical-units-to-set-up-chimeric-antigen-receptor-t-cell-therapy-car-t-cells-based-on-the-recommendations-of-the-francophone-society-of-bone-marrow-transplantation-and-cellular-therapy-sfgm-tc
#19
Ibrahim Yakoub-Agha
The Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) hold its eighth practice harmonization workshops on September 2017. In a workshop dedicated to chimeric antigen receptor T-cell therapy (CAR T-cells), the society issued recommendations regarding the prerequisite for hematopoietic cellular therapy programs to set up CAR T-cell therapy. In this article we focused on the prerequisite needed, in France, for a hematopoietic transplantation unit to start a CAR T-cell program with industrial manufactured cells within investigational products or after market access authorization...
April 20, 2018: Current Research in Translational Medicine
https://www.readbyqxmd.com/read/29685383/next-generation-conditioning-for-bone-marrow-transplantation-paving-the-way-for-car-t-cell-based-conditioning
#20
EDITORIAL
Kevin G Haworth, Hans-Peter Kiem
No abstract text is available yet for this article.
April 20, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
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