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https://www.readbyqxmd.com/read/28630092/characterization-of-high-avidity-cytomegalovirus-specific-t-cells-with-differential-tetramer-binding-coappearing-after-allogeneic-stem-cell-transplantation
#1
Justyna Ogonek, Kriti Verma, Christian Schultze-Florey, Pavankumar Varanasi, Susanne Luther, Patrick Schweier, Wolfgang Kühnau, Gudrun Göhring, Elke Dammann, Michael Stadler, Arnold Ganser, Ulrike Koehl, Christian Koenecke, Eva M Weissinger, Lothar Hambach
CMV reactivation is a major complication after allogeneic stem cell transplantation (SCT). Immune reconstitution of CMV-specific CTLs (CMV-CTLs) is essential for virus control. During CMV-CTL monitoring using mutated HLA/CMV tetramers selectively detecting high-avidity T cells, we observed coappearance of CMV-CTLs with low (CMV tet(low) CTLs) and high tetramer binding (CMV tet(high) CTLs) in 53/115 CMV IgG(+) patients stem cell transplanted from CMV IgG(+) donors. However, the relevance of these coappearing differentially tetramer binding ("dual") CMV-CTLs was unclear...
June 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28630090/t-cell-transcriptomes-from-paroxysmal-nocturnal-hemoglobinuria-patients-reveal-novel-signaling-pathways
#2
Kohei Hosokawa, Sachiko Kajigaya, Keyvan Keyvanfar, Wangmin Qiao, Yanling Xie, Danielle M Townsley, Xingmin Feng, Neal S Young
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disorder originating from hematopoietic stem cells and is a life-threating disease characterized by intravascular hemolysis, bone marrow (BM) failure, and venous thrombosis. The etiology of PNH is a somatic mutation in the phosphatidylinositol glycan class A gene (PIG-A) on the X chromosome, which blocks synthesis of the glycolipid moiety and causes deficiency in GPI-anchored proteins. PNH is closely related to aplastic anemia, in which T cells mediate destruction of BM...
June 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28623617/decrease-in-adult-neurogenesis-and-neuroinflammation-are-involved-in-spatial-memory-impairment-in-the-streptozotocin-induced-model-of-sporadic-alzheimer-s-disease-in-rats
#3
Taysa Bervian Bassani, Jéssica M Bonato, Meira M F Machado, Valentín Cóppola-Segovia, Eric L R Moura, Silvio M Zanata, Rúbia M M W Oliveira, Maria A B F Vital
Early impairments in cerebral glucose metabolism and insulin signaling pathways may participate in the pathogenesis of the sporadic form of Alzheimer's disease (sAD). Intracerebroventricular (ICV) injections of low doses of streptozotocin (STZ) are used to mimic sAD and study these alterations in rodents. Streptozotocin causes impairments in insulin signaling and has been reported to trigger several alterations in the brain, such as oxidative stress, neuroinflammation, and dysfunctions in adult neurogenesis, which may be involved in cognitive decline and are features of human AD...
June 16, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28623251/highly-functional-t-cell-receptor-repertoires-are-abundant-in-stem-memory-t-cells-and-highly-shared-among-individuals
#4
Takahiko Miyama, Takakazu Kawase, Kazutaka Kitaura, Ren Chishaki, Masashi Shibata, Kumi Oshima, Hiroshi Hamana, Hiroyuki Kishi, Atsushi Muraguchi, Kiyotaka Kuzushima, Hiroh Saji, Tadasu Shin-I, Ryuji Suzuki, Tatsuo Ichinohe
To expand our knowledge of the ontogeny of the T-cell receptor (TCR) repertoire of antigen-specific T-cell subsets, we combined next-generation deep sequencing and single-cell multiplex clonotype analysis to evaluate the diversity and frequency of paired TCRs, their functions and whether clonotypic TCRs are shared among different individuals. Using an HLA-A*02-restricted cytomegalovirus (CMV) pp65-derived immunogenic peptide, we found that the more dominant pp65-specific TCR clonotypes in the blood of healthy donors have higher binding affinities for the CMV peptide and arise from clonotypes that are highly shared among individuals...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28623139/the-co-expression-of-neogenin-with-sox2-in-hippocampal-neurons
#5
Namgue Hong, Mi-Hye Kim, Churl K Min, Hee Jung Kim, Jae Ho Lee
Dementia has been shown to be closely related with neuronal degeneration and/or a decrease in the activity of neural stem cells in many brain regions, including the hippocampus. It has been recently established that Neogenin is involved in the cell fate determination by regulating Oct3/4, SOX and Nanog, notable embryonic cell markers, expressions in pre-implantation mouse embryos. Further, Neogenin expression at both mRNA and protein levels is manifest in many brain regions in mice, but it remains unclear whether Neogenin expression is prerequisite for the maintenance of neural stem cells, particularly, playing a critical role in the hippocampus, a brain region known to be involved in memory generation and consolidation...
June 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28620836/sox2-immunity-and-tissue-resident-memory-in-children-and-young-adults-with-glioma
#6
Juan C Vasquez, Anita Huttner, Lin Zhang, Asher Marks, Amy Chan, Joachim M Baehring, Kristopher T Kahle, Kavita M Dhodapkar
Therapies targeting immune checkpoints are effective in tumors with a high mutation burden that express multiple neo-antigens. However, glial tumors including those seen in children carry fewer mutations and there is an unmet need to identify new antigenic targets of anti-tumor immunity. SOX2 is an embryonal stem cell antigen implicated in the biology of glioma initiating cells. Expression of SOX2 by pediatric glial tumors and the capacity of the immune system in these patients to recognize SOX2 has not been previously studied...
June 15, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28614804/in-vivo-kinetics-and-nonradioactive-imaging-of-rapidly-proliferating-cells-in-graft-versus-host-disease
#7
Nataliya P Buxbaum, Donald E Farthing, Natella Maglakelidze, Martin Lizak, Hellmut Merkle, Andrea C Carpenter, Brittany U Oliver, Veena Kapoor, Ehydel Castro, Gregory A Swan, Liliane M Dos Santos, Nicolas J Bouladoux, Catherine V Bare, Francis A Flomerfelt, Michael A Eckhaus, William G Telford, Yasmine Belkaid, Remy J Bosselut, Ronald E Gress
Hematopoietic stem cell transplantation (HSCT) offers a cure for cancers that are refractory to chemotherapy and radiation. Most HSCT recipients develop chronic graft-versus-host disease (cGVHD), a systemic alloimmune attack on host organs. Diagnosis is based on clinical signs and symptoms, as biopsies are risky. T cells are central to the biology of cGVHD. We found that a low Treg/CD4+ T effector memory (Tem) ratio in circulation, lymphoid, and target organs identified early and established mouse cGVHD. Using deuterated water labeling to measure multicompartment in vivo kinetics of these subsets, we show robust Tem and Treg proliferation in lymphoid and target organs, while Tregs undergo apoptosis in target organs...
June 15, 2017: JCI Insight
https://www.readbyqxmd.com/read/28607914/reconstitution-of-adaptive-immunity-after-umbilical-cord-blood-transplantation-impact-on-infectious-complications
#8
REVIEW
Sophie Servais, Muriel Hannon, Régis Peffault de Latour, Gérard Socie, Yves Beguin
In comparison with allogeneic stem cell transplantation (alloHSCT) with other stem cell sources, umbilical cord blood transplantation (UCBT) was traditionally associated with increased risk of infections, particularly during the first 3 months after transplantation. Longitudinal studies of immune monitoring reported peculiar patterns of T- and B-cell recovery in the peripheral blood of UCB recipients during the first months post-transplantation. Overall, current data suggest delayed reconstitution of naive and memory CD4(+) and CD8(+) T-cell pools after UCBT...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28600802/mtorc1-and-mtorc2-as-regulators-of-cell-metabolism-in-immunity
#9
REVIEW
Monika Linke, Stephanie Deborah Fritsch, Nyamdelger Sukhbaatar, Markus Hengstschläger, Thomas Weichhart
The mechanistic target of rapamycin (mTOR) pathway is an evolutionarily conserved signaling pathway that senses intra- and extracellular nutrients, growth factors, and pathogen-associated molecular patterns to regulate the function of innate and adaptive immune cell populations. In this Review, we focus on the role of the mTOR complex 1 (mTORC1) and mTORC2 in the regulation of the cellular energy metabolism of these immune cells to regulate and support immune responses. In this regard, mTORC1 and mTORC2 generally promote an anabolic response by stimulating protein synthesis, glycolysis, mitochondrial functions, and lipid synthesis to influence proliferation and survival, effector and memory responses, innate training and tolerance as well as hematopoietic stem cell maintenance and differentiation...
June 10, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28589443/metformin-a-future-therapy-for-neurodegenerative-diseases
#10
REVIEW
Magdalena Markowicz-Piasecka, Joanna Sikora, Aleksandra Szydłowska, Agata Skupień, Elżbieta Mikiciuk-Olasik, Kristiina M Huttunen
Type 2 diabetes mellitus (T2DM) is a complex, chronic and progressive metabolic disease, which is characterized by relative insulin deficiency, insulin resistance, and high glucose levels in blood. Esteemed published articles and epidemiological data exhibit an increased risk of developing Alzheimer's disease (AD) in diabetic pateints. Metformin is the most frequently used oral anti-diabetic drug, which apart from hypoglycaemic activity, improves serum lipid profiles, positively influences the process of haemostasis, and possesses anti-inflammatory properties...
June 6, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28580186/mash1-dependent-notch-signaling-pathway-regulates-gabaergic-neuron-like-differentiation-from-bone-marrow-derived-mesenchymal-stem-cells
#11
Qianfa Long, Qiang Luo, Kai Wang, Adrian Bates, Ashok K Shetty
GABAergic neuronal cell grafting has promise for treating a multitude of neurological disorders including epilepsy, age-related memory dysfunction, Alzheimer's disease and schizophrenia. However, identification of an unlimited source of GABAergic cells is critical for advancing such therapies. Our previous study implied that reprogramming of bone marrow-derived mesenchymal stem cells (BMSCs) through overexpression of the Achaete-scute homolog 1 (Ascl1, also called Mash1) could generate GABAergic neuron-like cells...
May 2017: Aging and Disease
https://www.readbyqxmd.com/read/28576310/the-paracrine-effect-of-cobalt-chloride-on-bmscs-during-cognitive-function-rescue-in-the-hibd-rat
#12
Ying Dai, Wendi Li, Min Zhong, Jie Chen, Qian Cheng, Youxue Liu, Tingyu Li
Hypoxia-ischemia (HI)-induced perinatal encephalopathy frequently causes chronic neurological morbidities and acute mortality. Bone mesenchymal stem cell (BMSC) transplantation could potentially promote functional and anatomical recovery of ischemic tissue. In vitro hypoxic preconditioning is an effective strategy to improve the survival of BMSCs in ischemic tissue. In this study, cobalt chloride (CoCl2) preconditioned medium from BMSC cultures was injected into the left lateral ventricle of HI rats using a micro-osmotic pump at a flow rate 1...
May 30, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28574833/new-interleukin-15-superagonist-il-15sa-significantly-enhances-graft-versus-tumor-activity
#13
Cavan P Bailey, Tulin Budak-Alpdogan, Christopher T Sauter, Michelle M Panis, Cihangir Buyukgoz, Emily K Jeng, Hing C Wong, Neal Flomenberg, Onder Alpdogan
Interleukin-15 (IL-15) is a potent cytokine that increases CD8+ T and NK cell numbers and function in experimental models. However, obstacles remain in using IL-15 therapeutically, specifically its low potency and short in vivo half-life. To help overcome this, a new IL-15 superagonist complex comprised of an IL-15N72D mutation and IL-15RαSu/Fc fusion (IL-15SA, also known as ALT-803) was developed. IL-15SA exhibits a significantly longer serum half-life and increased in vivo activity against various tumors...
May 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28554227/modulating-epigenetic-memory-through-vitamins-and-tet-implications-for-regenerative-medicine-and-cancer-treatment
#14
Timothy A Hore
Vitamins A and C represent unrelated sets of small molecules that are essential to the human diet and have recently been shown to intensify erasure of epigenetic memory in naive embryonic stem cells. These effects are driven by complementary enhancement of the ten-eleven translocation (TET) demethylases - vitamin A stimulates TET expression, whereas vitamin C potentiates TET catalytic activity. Vitamin A and C cosupplementation synergistically enhances reprogramming of differentiated cells to the naive state, but overuse may exaggerate instability of imprinted genes...
June 2017: Epigenomics
https://www.readbyqxmd.com/read/28550199/comprehensive-approach-for-identifying-the-t-cell-subset-origin-of-cd3-and-cd28-antibody-activated-chimeric-antigen-receptor-modified-t-cells
#15
Michael Schmueck-Henneresse, Bilal Omer, Thomas Shum, Haruko Tashiro, Maksim Mamonkin, Natalia Lapteva, Sandhya Sharma, Lisa Rollins, Gianpietro Dotti, Petra Reinke, Hans-Dieter Volk, Cliona M Rooney
The outcome of therapy with chimeric Ag receptor (CAR)-modified T cells is strongly influenced by the subset origin of the infused T cells. However, because polyclonally activated T cells acquire a largely CD45RO(+)CCR7(-) effector memory phenotype after expansion, regardless of subset origin, it is impossible to know which subsets contribute to the final T cell product. To determine the contribution of naive T cell, memory stem T cell, central memory T cell, effector memory T cell, and terminally differentiated effector T cell populations to the CD3 and CD28-activated CAR-modified T cells that we use for therapy, we followed the fate and function of individually sorted CAR-modified T cell subsets after activation with CD3 and CD28 Abs (CD3/28), transduction and culture alone, or after reconstitution into the relevant subset-depleted population...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28548278/neuropeptide-s-precursor-knockout-mice-display-memory-and-arousal-deficits
#16
Xiaobin Liu, Wei Si, Celia Garau, Kay Jüngling, Hans-Christian Pape, Stefan Schulz, Rainer K Reinscheid
Activation of neuropeptide S (NPS) signaling has been found to produce arousal, wakefulness, anxiolytic-like behaviors, and enhanced memory formation. In order to further study physiological functions of the NPS system, we generated NPS precursor knockout mice by homologous recombination in embryonic stem cells. NPS(-/-) mice were viable, fertile, and anatomically normal, when compared to their wild-type and heterozygous littermates. The total number of NPS neurons-although no longer synthesizing the peptide - was not affected by the knockout, as analyzed in NPS(-/-) /NPS(EGFP) double transgenic mice...
May 26, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28530241/notch-mediated-conversion-of-activated-t-cells-into-stem-cell-memory-like-t-cells-for-adoptive-immunotherapy
#17
Taisuke Kondo, Rimpei Morita, Yuumi Okuzono, Hiroko Nakatsukasa, Takashi Sekiya, Shunsuke Chikuma, Takashi Shichita, Mitsuhiro Kanamori, Masato Kubo, Keiko Koga, Takahiro Miyazaki, Yoshiaki Kassai, Akihiko Yoshimura
Adoptive T-cell immunotherapy is a promising approach to cancer therapy. Stem cell memory T (TSCM) cells have been proposed as a class of long-lived and highly proliferative memory T cells. CD8(+) TSCM cells can be generated in vitro from naive CD8(+) T cells via Wnt signalling; however, methods do not yet exist for inducing TSCM cells from activated or memory T cells. Here, we show a strategy for generating TSCM-like cells in vitro (iTSCM cells) from activated CD4(+) and CD8(+) T cells in mice and humans by coculturing with stromal cells that express a Notch ligand...
May 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28529527/skeletal-muscle-cell-induction-from-pluripotent-stem-cells
#18
REVIEW
Yusaku Kodaka, Gemachu Rabu, Atsushi Asakura
Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have the potential to differentiate into various types of cells including skeletal muscle cells. The approach of converting ESCs/iPSCs into skeletal muscle cells offers hope for patients afflicted with the skeletal muscle diseases such as the Duchenne muscular dystrophy (DMD). Patient-derived iPSCs are an especially ideal cell source to obtain an unlimited number of myogenic cells that escape immune rejection after engraftment. Currently, there are several approaches to induce differentiation of ESCs and iPSCs to skeletal muscle...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28528185/simvastatin-ameliorate-memory-deficits-and-inflammation-in-clinical-and-mouse-model-of-alzheimer-s-disease-via-modulating-the-expression-of-mir-106b
#19
Wenzhong Huang, Zhenyu Li, Liandong Zhao, Wei Zhao
BACKGROUND: Alzheimer's disease (AD) as a neurodegenerative brain disorder is a devastating pathology leading to disastrous cognitive impairments and dementia, and several studies have shown that AD is closely related to the inflammation, so anti-inflammatory treatment may provide therapeutic benefits. In this study, the effect of simvastatin on inflammation was investigated and the underlying mechanisms were explored. METHODS: First, we tested the effect of simvastatin on AD in clinical research...
May 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28516108/what-is-car-doing-in-the-middle-of-the-adult-neurogenic-road
#20
COMMENT
Sara Salinas, Felix Junyent, Nathalie Coré, Harold Cremer, Eric J Kremer
The molecular and cellular basis of adult neurogenesis has attracted considerable attention for fundamental and clinical applications because neural stem cells and newborn neurons may, one day, be harnessed to replace neurons and allow cognitive improvement in the diseased brain. In rodents, neural progenitors are located in the dentate gyrus and the sub/periventricular zone. In the dentate gyrus the generation of newborn neurons is associated with plasticity, including regulation of memory. The role of subventricular zone neural precursors that migrate to the olfactory bulb is less characterized...
2017: Neurogenesis (Austin, Tex.)
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