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Memory Stem T-Cells

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https://www.readbyqxmd.com/read/29051183/development-of-t-cell-immunotherapy-for-hematopoietic-stem-cell-transplantation-recipients-at-risk-of-leukemia-relapse
#1
Robson G Dossa, Tanya Cunningham, Daniel Sommermeyer, Indira Medina-Rodriguez, Melinda A Biernacki, Kimberly Foster, Marie Bleakley
Leukemia relapse remains the major cause of allogeneic hematopoietic stem cell transplantation (HCT) failure and the prognosis for patients with post-HCT relapse is poor. There is compelling evidence that potent selective anti-leukemic effects can be delivered by donor T cells specific for particular minor histocompatibility (H) antigens. Thus, T cell receptors (TCR) isolated from minor H antigen-specific T cells represent an untapped resource for developing targeted T cell immunotherapy to manage post-HCT leukemic relapse...
October 19, 2017: Blood
https://www.readbyqxmd.com/read/29045388/inflammatory-memory-sensitizes-skin-epithelial-stem-cells-to-tissue-damage
#2
Shruti Naik, Samantha B Larsen, Nicholas C Gomez, Kirill Alaverdyan, Ataman Sendoel, Shaopeng Yuan, Lisa Polak, Anita Kulukian, Sophia Chai, Elaine Fuchs
The skin barrier is the body's first line of defence against environmental assaults, and is maintained by epithelial stem cells (EpSCs). Despite the vulnerability of EpSCs to inflammatory pressures, neither the primary response to inflammation nor its enduring consequences are well understood. Here we report a prolonged memory to acute inflammation that enables mouse EpSCs to hasten barrier restoration after subsequent tissue damage. This functional adaptation does not require skin-resident macrophages or T cells...
October 18, 2017: Nature
https://www.readbyqxmd.com/read/29035156/cd4-t-memory-stem-cells-correlate-with-disease-progression-in-chronically-hiv-1-infected-patients
#3
Xiaofan Lu, Bingbing Song, Wenjia Weng, Huan Xia, Bin Su, Hao Wu, Tong Zhang, Wei Li, Yanqing Gao
Recently identified T memory stem (Tscm) cells have stem-cell-like properties, including long lifespan, self-renewal capacity, and multipotency to differentiate into other memory T cell types. In the study of simian immunodeficiency virus (SIV) infection, selective depletion of CCR5(+)CD4(+) Tscm cells and the high proliferation rate of these cells are believed to be responsible for the pathogenesis of SIV-infected rhesus macaques. Here, we conducted a cohort study to investigate the influence of chronic human immunodeficiency virus (HIV)-1 infection on CD4(+) Tscm cell homeostasis, and the effect of antiretroviral therapy (ART) on CD4(+) Tscm cells...
October 16, 2017: Viral Immunology
https://www.readbyqxmd.com/read/29021396/quiescence-promotes-latent-hiv-infection-and-resistance-to-reactivation-from-latency-with-histone-deacetylase-inhibitors
#4
Mark M Painter, Thomas D Zaikos, Kathleen L Collins
Human immunodeficiency virus type-1 (HIV-1) establishes transcriptionally silent latent infections in many cell types, including resting memory T cells and hematopoietic stem and progenitor cells (HSPCs), which allow the virus to persist in infected individuals despite antiretroviral therapy. Developing in vitro models of HIV-1 latency that recapitulate the characteristics of latently-infected cells in vivo is crucial to identifying and developing effective latency-reversing therapies. HSPCs exist in a quiescent state in vivo, and quiescence is correlated with latent infections in T cells...
October 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28994018/memory-cd4-t-cell-subsets-in-tumor-draining-lymph-nodes-of-breast-cancer-patients-a-focus-on-t-stem-cell-memory-cells
#5
Yasmin Vahidi, Zahra Faghih, Abdol-Rasoul Talei, Mehrnoosh Doroudchi, Abbas Ghaderi
BACKGROUND: The compartments of memory T cells play a fundamental role in the immune system by substantiating specific and acquired immunity. A new subset of memory cells, T stem cell memory (TSCM) cells, with stem cell-like properties, a high capacity to proliferate, a long survival, and an ability to differentiate into all effector and memory cells has recently been introduced. In the present study, we aimed to determine the frequency of CD4(+) TSCM and other T memory cell subsets in tumor draining lymph nodes of breast cancer patients...
October 9, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28979262/cd28-blockade-ex-vivo-induces-alloantigen-specific-immune-tolerance-but-preserves-t-cell-pathogen-reactivity
#6
Barbara Dillinger, Sarah Ahmadi-Erber, Klara Soukup, Angela Halfmann, Silke Schrom, Bernard Vanhove, Peter Steinberger, Rene Geyeregger, Stephan Ladisch, Alexander Michael Dohnal
Donor T-cells contribute to reconstitution of protective immunity after allogeneic hematopoietic stem cell transplantation (HSCT) but must acquire specific tolerance against recipient alloantigens to avoid life-threatening graft-versus-host disease (GvHD). Systemic immunosuppressive drugs may abrogate severe GvHD, but this also impedes memory responses to invading pathogens. Here, we tested whether ex vivo blockade of CD28 co-stimulation can enable selective T-cell tolerization to alloantigens by facilitating CD80/86-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) signaling...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28935847/cd56bright-nk-regulatory-cells-in-filgrastim-primed-donor-blood-or-marrow-products-regulate-chronic-gvhd-cbmtg-randomized-0601-study-results
#7
Amina Kariminia, Sabine Ivison, Bernard Ng, Jacob Rozmus, Susanna Sung, Avani Varshney, Mahmoud Aljurf, Silvy Lachance, Irwin Walker, Cindy Toze, Jeff Lipton, Stephanie J Lee, Jeff Szer, Richard Doocey, Ian Lewis, Clayton Smith, Naeen Chaudhri, Megan K Levings, Raewyn Broady, Gerald Devins, David Szwajcer, Ronan Foley, Sara Mostafavi, Steven Pavletic, Donna A Wall, Stephen Couban, Tony Panzarella, Kirk R Schultz
Randomized trials have conclusively shown higher rates of chronic graft-versus-host disease with filgrastim-stimulated apheresis peripheral blood as a donor source than unstimulated bone marrow. The Canadian Blood and Marrow Transplant Group conducted a phase 3 study of adults who received either filgrastim-stimulated apheresis peripheral blood or filgrastim-stimulated bone marrow from human leukocyte antigen-identical sibling donors. Because all donors received the identical filgrastim dosing schedule, this study allowed for a controlled evaluation of the impact of stem cell source on development of chronic graft-versus-host disease...
September 21, 2017: Haematologica
https://www.readbyqxmd.com/read/28934393/neurofibromatosis-type-1-alternative-splicing-is-a-key-regulator-of-ras-erk-signaling-and-learning-behaviors-in-mice
#8
Hieu T Nguyen, Melissa N Hinman, Xuan Guo, Alok Sharma, Hiroyuki Arakawa, Guangbin Luo, Hua Lou
Appropriate activation of the Ras/extracellular signal-regulated kinase (ERK) protein signaling cascade within the brain is crucial for optimal learning and memory. One key regulator of this cascade is the Nf1 Ras GTPase activating protein (RasGAP), which attenuates Ras/ERK signaling by converting active Ras is bound to guanosine triphosphate, activating Ras into inactive Ras is bound to guanosine diphosphate, inactivating Ras. A previous study using embryonic stem cells and embryonic stem cell-derived neurons indicated that Nf1 RasGAP activity is modulated by the highly regulated alternative splicing of Nf1 exon 23a...
October 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28904691/il-21-augments-rapamycin-in-expansion-of-alpha-fetoprotein-antigen-specific-stem-cell-like-memory-t-cells-in-vitro
#9
Victor Tunje Jeza, Xiaoyi Li, Jun Chen, Zhihui Liang, Adem Onago Aggrey, Xiongwen Wu
INTRODUCTION: Alloreactive tumor specific T cells are important arsenals of the adaptive immune system in the fight against tumors. However, stem cell-like memory T cells (Tscm) provide the key to effective elimination of tumor cells. Methods for generating these T cell subsets already exist. However, they could be made more efficient. Further, they are expensive and unattainable to the resource poor laboratories. In this regard, we are hereby describing a novel in vitro allogeneic co-culture method for raising allo-restricted tumor specific Tscm cells that we developed...
2017: Pan African Medical Journal
https://www.readbyqxmd.com/read/28904110/the-chromatin-accessibility-signature-of-human-immune-aging-stems-from-cd8-t-cells
#10
Duygu Ucar, Eladio J Márquez, Cheng-Han Chung, Radu Marches, Robert J Rossi, Asli Uyar, Te-Chia Wu, Joshy George, Michael L Stitzel, A Karolina Palucka, George A Kuchel, Jacques Banchereau
Aging is linked to deficiencies in immune responses and increased systemic inflammation. To unravel the regulatory programs behind these changes, we applied systems immunology approaches and profiled chromatin accessibility and the transcriptome in PBMCs and purified monocytes, B cells, and T cells. Analysis of samples from 77 young and elderly donors revealed a novel and robust aging signature in PBMCs, with simultaneous systematic chromatin closing at promoters and enhancers associated with T cell signaling and a potentially stochastic chromatin opening mostly found at quiescent and repressed sites...
October 2, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28861081/14%C3%A2-years-after-discovery-clinical-follow-up-on-15-patients-with-inducible-co-stimulator-deficiency
#11
Johanna Schepp, Janet Chou, Andrea Skrabl-Baumgartner, Peter D Arkwright, Karin R Engelhardt, Sophie Hambleton, Tomohiro Morio, Ekkehard Röther, Klaus Warnatz, Raif Geha, Bodo Grimbacher
BACKGROUND: Inducible co-stimulator (ICOS) deficiency was the first monogenic defect reported to cause common variable immunodeficiency (CVID)-like disease in 2003. Since then, 16 patients have been reported worldwide with an increasing range of clinical phenotypes. OBJECTIVE: We sought to compare the clinical and immunological phenotype and provide clinical follow-up and therapeutic approaches for treating ICOS-deficient patients. METHODS: We describe the clinical and laboratory data of 15 patients with available clinical data...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28855514/hit-and-run-programming-of-therapeutic-cytoreagents-using-mrna-nanocarriers
#12
H F Moffett, M E Coon, S Radtke, S B Stephan, L McKnight, A Lambert, B L Stoddard, H P Kiem, M T Stephan
Therapies based on immune cells have been applied for diseases ranging from cancer to diabetes. However, the viral and electroporation methods used to create cytoreagents are complex and expensive. Consequently, we develop targeted mRNA nanocarriers that are simply mixed with cells to reprogram them via transient expression. Here, we describe three examples to establish that the approach is simple and generalizable. First, we demonstrate that nanocarriers delivering mRNA encoding a genome-editing agent can efficiently knock-out selected genes in anti-cancer T-cells...
August 30, 2017: Nature Communications
https://www.readbyqxmd.com/read/28851693/the-antitumor-effects-of-vaccine-activated-cd8-t-cells-associate-with-weak-tcr-signaling-and-induction-of-stem-like-memory-t-cells
#13
Sha Wu, Wei Zhu, Yibing Peng, Lan Wang, Yuan Hong, Lei Huang, Dayong Dong, Junping Xie, Todd Merchen, Edward Kruse, Zong Sheng Guo, David Bartlett, Ning Fu, Yukai He
To understand why vaccine-activated tumor-specific T cells often fail to generate antitumor effects, we studied two α-fetoprotein-specific CD8(+) T cells (Tet499 and Tet212) that had different antitumor effects. We found that Tet499 required high antigen doses for reactivation, but could survive persistent antigen stimulation and maintain their effector functions. In contrast, Tet212 had a low threshold of reactivation, but underwent exhaustion and apoptosis in the presence of persistent antigen. In vivo, Tet499 cells expanded more than Tet212 upon reencountering antigen and generated stronger antitumor effects...
October 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28837861/klotho-regulates-postnatal-neurogenesis-and-protects-against-age-related-spatial-memory-loss
#14
Ann M Laszczyk, Stephanie Fox-Quick, Hai T Vo, Dailey Nettles, Phyllis C Pugh, Linda Overstreet-Wadiche, Gwendalyn D King
Although the absence of the age-regulating klotho protein causes klotho-deficient mice to rapidly develop cognitive impairment and increasing klotho enhances hippocampal-dependent memory, the cellular effects of klotho that mediate hippocampal-dependent memory function are unknown. Here, we show premature aging of the klotho-deficient hippocampal neurogenic niche as evidenced by reduced numbers of neural stem cells, decreased proliferation, and impaired maturation of immature neurons. Klotho-deficient neurospheres show reduced proliferation and size that is rescued by supplementation with shed klotho protein...
November 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28827761/copy-number-elevation-of-22q11-2-genes-arrests-the-developmental-maturation-of-working-memory-capacity-and-adult-hippocampal-neurogenesis
#15
S Boku, T Izumi, S Abe, T Takahashi, A Nishi, H Nomaru, Y Naka, G Kang, M Nagashima, A Hishimoto, S Enomoto, G Duran-Torres, K Tanigaki, J Zhang, K Ye, S Kato, P T Männistö, K Kobayashi, N Hiroi
Working memory capacity, a critical component of executive function, expands developmentally from childhood through adulthood. Anomalies in this developmental process are seen in individuals with autism spectrum disorder (ASD), schizophrenia and intellectual disabilities (ID), implicating this atypical process in the trajectory of developmental neuropsychiatric disorders. However, the cellular and neuronal substrates underlying this process are not understood. Duplication and triplication of copy number variants of 22q11...
August 22, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28826528/chemokine-driven-cd4-t-cell-homing-new-concepts-and-recent-advances
#16
Carly E Gregor, Jade Foeng, Iain Comerford, Shaun R McColl
CD4(+) T cells are critical regulators of the adaptive immune system and have diverse roles in regulating responses to the broad array of microbes encountered. Appropriate execution of their effector function requires precise and coordinated migration of these cells to specific lymphoid niches and peripheral sites. This migration is largely controlled by dynamic expression of chemokine receptors and the discrete functions of distinct subsets of CD4(+) T cells can often be determined from their expression of specific chemokine receptors...
2017: Advances in Immunology
https://www.readbyqxmd.com/read/28818684/t-cell-mediated-rejection-of-human-cd34-cells-is-prevented-by-costimulatory-blockade-in-a-xenograft-model
#17
Annie L Oh, Dolores Mahmud, Benedetta Nicolini, Nadim Mahmud, Vitalyi Senyuk, Pritesh R Patel, Elisa Bonetti, Mario Arpinati, James L M Ferrara, Damiano Rondelli
A xenograft model of stem cell rejection was developed by co-transplantating human CD34(+) and allogeneic CD3(+) T cells into NOD-scid ɣ-chain(null) mice. T cells caused graft failure when transplanted at any CD34/CD3 ratio between 1:50 and 1:.1. Kinetics experiments showed that 2 weeks after transplantation CD34(+) cells engrafted the marrow and T cells expanded in the spleen. Then, at 4 weeks only memory T cells populated both sites and rejected CD34(+) cells. Blockade of T cell costimulation was tested by injecting the mice with abatacept (CTLA4-IgG1) from day -1 to +27 (group A), from day -1 to +13 (group B), or from day +14 to +28 (group C)...
August 14, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28801292/-oxidized-low-density-lipoprotein-modulates-differentiation-of-murine-memory-cd8-t-cell-subpopulations
#18
Hua Zheng, Ze-Hang Lin, Yan-Mei Zhang, Chen-Fei Zhou, Xuan Liu, Sha Wu
OBJECTIVE: To investigate effect of oxidized low-density lipoprotein (ox-LDL) on memory CD8(+) T cell subpopulation differentiation in mice with autoimmune diabetes. METHODS: Cultured splenic CD8(+) T cells from pre-diabetic NOD mice isolated with magnetic beads were treated with 30 µg/mL ox-LDL and 10 U/mL interleukin-2 (IL-2) for 24 h and the control cells were treated with IL-2 only. Flow cytometry was used to determine the percentage of splenic CD8(+)IFN-γ(+) T cells, expressions of CD8, CD44 and CD62L on the T cells, and the activation of T cell factor-1 (TCF-1) and STAT-3...
August 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28783708/preferential-induction-of-cross-group-influenza-a-hemagglutinin-stem-specific-memory-b-cells-after-h7n9-immunization-in-humans
#19
Sarah F Andrews, M Gordon Joyce, Michael J Chambers, Rebecca A Gillespie, Masaru Kanekiyo, Kwanyee Leung, Eun Sung Yang, Yaroslav Tsybovsky, Adam K Wheatley, Michelle C Crank, Jeffrey C Boyington, Madhu S Prabhakaran, Sandeep R Narpala, Xuejun Chen, Robert T Bailer, Grace Chen, Emily Coates, Peter D Kwong, Richard A Koup, John R Mascola, Barney S Graham, Julie E Ledgerwood, Adrian B McDermott
Antigenic drift and shift of influenza strains underscore the need for broadly protective influenza vaccines. One strategy is to design immunogens that elicit B cell responses against conserved epitopes on the hemagglutinin (HA) stem. To better understand the elicitation of HA stem-targeted B cells to group 1 and group 2 influenza subtypes, we compared the memory B cell response to group 2 H7N9 and group 1 H5N1 vaccines in humans. Upon H7N9 vaccination, almost half of the HA stem-specific response recognized the group 1 and group 2 subtypes, whereas the response to H5N1 was largely group 1-specific...
July 14, 2017: Science Immunology
https://www.readbyqxmd.com/read/28758191/interleukin-27-signalling-induces-stem-cell-antigen-1-expression-in-t-lymphocytes-in%C3%A2-vivo
#20
Zhihao Liu, Lisha Wu, Jing Zhu, Xiaotong Zhu, Jianmin Zhu, Jin-Qing Liu, Jianchao Zhang, Jonathan P Davis, Sanjay Varikuti, Abhay R Satoskar, Jie Zhou, Ming-Song Li, Xue-Feng Bai
Stem cell antigen-1 (Sca-1/Ly6A/E) is a cell surface glycoprotein that is often used as a biomarker for stem cells and cell stemness. However, it is not clear what factors can directly induce the expression of Sca-1/Ly6A/E in T lymphocytes in vivo, and if induction of Sca-1 is associated with T cell stemness. In this study, we show that interleukin-27 (IL-27), a member of the IL-12 family of cytokines, directly induces Sca-1 expression in T cells in vivo. We found that mice-deficient for IL-27 (either P28 or EBI3) or its signalling (IL-27Rα) had profound reduction of Sca-1 expression in naive (CD62L(+)  CD44(-) ), memory (CD62L(+)  CD44(+) ) and effector (CD62L(-)  CD44(+) ) T cells...
July 31, 2017: Immunology
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