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Memory Stem T-Cells

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https://www.readbyqxmd.com/read/27914462/recombinant-mhc-tetramers-for-isolation-of-virus-specific-cd8-cells-from-healthy-donors-potential-approach-for-cell-therapy-of-posttransplant-cytomegalovirus-infection
#1
A S Vdovin, S Y Filkin, P R Yefimova, S A Sheetikov, N M Kapranov, Y O Davydova, E S Egorov, E G Khamaganova, M Y Drokov, L A Kuzmina, E N Parovichnikova, G A Efimov, V G Savchenko
Patients undergoing allogeneic hematopoietic stem cell transplantation have a high risk of cytomegalovirus reactivation, which in the absence of T-cell immunity can result in the development of an acute inflammatory reaction and damage of internal organs. Transfusion of the virus-specific donor T-lymphocytes represents an alternative to a highly toxic and often ineffective antiviral therapy. Potentially promising cell therapy approach comprises transfusion of cytotoxic T-lymphocytes, specific to the viral antigens, immediately after their isolation from the donor's blood circulation without any in vitro expansion...
November 2016: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/27894837/cd4-virtual-memory-antigen-inexperienced-t-cells-reside-in-the-na%C3%A3-ve-regulatory-and-memory-t-cell-compartments-at-similar-frequencies-implications-for-autoimmunity
#2
Alina I Marusina, Yoko Ono, Alexander A Merleev, Michiko Shimoda, Hiromi Ogawa, Elizabeth A Wang, Kayo Kondo, Laura Olney, Guillaume Luxardi, Yoshinori Miyamura, Tilahun D Yilma, Itzel Bustos Villalobos, Jennifer W Bergstrom, Daniel G Kronenberg, Athena M Soulika, Iannis E Adamopoulos, Emanual Maverakis
It is widely accepted that central and effector memory CD4(+) T cells originate from naïve T cells after they have encountered their cognate antigen in the setting of appropriate co-stimulation. However, if this were true the diversity of T cell receptor (TCR) sequences within the naïve T cell compartment should be far greater than that of the memory T cell compartment, which is not supported by TCR sequencing data. Here we demonstrate that aged mice with far fewer naïve T cells, respond to the model antigen, hen eggwhite lysozyme (HEL), by utilizing the same TCR sequence as their younger counterparts...
November 25, 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27872103/rapid-and-continued-t-cell-differentiation-into-long-term-effector-and-memory-stem-cells-in-vaccinated-melanoma-patients
#3
Philippe Gannon, Petra Baumgaertner, Alexandre Huber, Emanuela M Iancu, Laurene Cagnon, Samia Abed-Maillard, Helene Maby-El Hajjami, Daniel E Speiser, Nathalie Rufer
PURPOSE: Cancer patients benefit increasingly from T cell-based therapies, such as adoptive T cell transfer, checkpoint blockade or vaccination. We have previously shown that serial vaccinations with Melan-AMART-126-35 peptide, CpG-B and IFA generated robust tumor-specific CD8 T cell responses in melanoma patients. Here, we describe the detailed kinetics of early- and long-term establishment of T cell frequency, differentiation (into memory and effector cells), poly-functionality and clonotype repertoire induced by vaccination...
November 21, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27863245/epigenetic-memory-underlies-cell-autonomous-heterogeneous-behavior-of-hematopoietic-stem-cells
#4
Vionnie W C Yu, Rushdia Z Yusuf, Toshihiko Oki, Juwell Wu, Borja Saez, Xin Wang, Colleen Cook, Ninib Baryawno, Michael J Ziller, Eunjung Lee, Hongcang Gu, Alexander Meissner, Charles P Lin, Peter V Kharchenko, David T Scadden
Stem cells determine homeostasis and repair of many tissues and are increasingly recognized as functionally heterogeneous. To define the extent of-and molecular basis for-heterogeneity, we overlaid functional, transcriptional, and epigenetic attributes of hematopoietic stem cells (HSCs) at a clonal level using endogenous fluorescent tagging. Endogenous HSC had clone-specific functional attributes over time in vivo. The intra-clonal behaviors were highly stereotypic, conserved under the stress of transplantation, inflammation, and genotoxic injury, and associated with distinctive transcriptional, DNA methylation, and chromatin accessibility patterns...
November 17, 2016: Cell
https://www.readbyqxmd.com/read/27861287/wnt-signaling-as-master-regulator-of-t-lymphocyte-responses-implications-for-transplant-therapy
#5
Frank J T Staal, Ramon Arens
T cell-mediated immune responses to the grafted tissues are the major reason for failed organ transplantation. The regulation of T cell responses is complex and involves major histocompatibility complex molecules on transplanted organs, cytokines, regulatory cells, and antigen-presenting cells. The evolutionary conserved Wnt signal transduction pathway has long been known for its importance in development of stem cells and immature T cells in the thymus. Recent evidence indicates the Wnt pathway as a master regulator of T cell immune responses via governing the balance between T helper 17/regulatory T cells and by regulating the formation of effector and memory cytotoxic CD8 T cell responses...
December 2016: Transplantation
https://www.readbyqxmd.com/read/27849617/tethered-il-15-augments-antitumor-activity-and-promotes-a-stem-cell-memory-subset-in-tumor-specific-t-cells
#6
Lenka V Hurton, Harjeet Singh, Amer M Najjar, Kirsten C Switzer, Tiejuan Mi, Sourindra Maiti, Simon Olivares, Brian Rabinovich, Helen Huls, Marie-Andrée Forget, Vrushali Datar, Partow Kebriaei, Dean A Lee, Richard E Champlin, Laurence J N Cooper
Adoptive immunotherapy retargeting T cells to CD19 via a chimeric antigen receptor (CAR) is an investigational treatment capable of inducing complete tumor regression of B-cell malignancies when there is sustained survival of infused cells. T-memory stem cells (TSCM) retain superior potential for long-lived persistence, but challenges exist in manufacturing this T-cell subset because they are rare among circulating lymphocytes. We report a clinically relevant approach to generating CAR(+) T cells with preserved TSCM potential using the Sleeping Beauty platform...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27828929/the-characteristics-of-naive-like-t-cells-in-tumor-infiltrating-lymphocytes-from-human-lung-cancer
#7
Si Yuan Sheng, Yong Gu, Chuan Gang Lu, Ying Ying Tang, Jian Yong Zou, Yu Qing Zhang, Rong Fu Wang, Hai Hong
Adoptive cell therapy using autologous tumor-infiltrating lymphocytes (TILs) or genetically modified lymphocytes from TILs is a new effective approach, but the application of TIL immunotherapy is still limited in many solid tumors. Knowledge of the classification and function of TILs is important to develop personalized immunotherapy with TILs in non-small lung cancer (NSCLC). In this study, we show the characteristics of T-cell subsets in TILs isolated from NSCLC. CD3 CD8 CD45RA T cells outnumbered CD3 CD4 CD45RA T cells in CD45RA TILs, but it was the opposite in CD45RO TILs...
January 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/27816648/mixed-t-cell-chimerism-after-allogeneic-hematopoietic-stem-cell-transplantation-for-severe-aplastic-anemia-using-an-alemtuzumab-containing-regimen-is-shaped-by-persistence-of-recipient-cd8-t-cells
#8
Francesco Grimaldi, Victoria Potter, Pilar Perez-Abellan, John P Veluchamy, Muhammad Atif, Rosemary Grain, Monica Sen, Steven Best, Nicholas Lea, Carmel Rice, Antonio Pagliuca, Ghulam J Mufti, Judith C W Marsh, Linda D Barber
Prevention of graft-versus-host disease (GVHD) is paramount for allogeneic hematopoietic stem cell transplantation (HSCT) to treat nonmalignant diseases. We previously reported that allogeneic HSCT for severe aplastic anemia (SAA) using the fludarabine, cyclophosphamide, and alemtuzumab (Campath-1H) (FCC) regimen is associated with a very low risk of GVHD and excellent clinical outcomes. We now report a single-center study of 45 patients with longer follow-up and investigation of lymphocyte recovery. Overall survival (OS) was 93%, and event-free survival (EFS) was 90...
November 2, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27814520/adult-neurogenesis-in-the-hippocampus-from-stem-cells-to-behavior
#9
REVIEW
J Tiago Gonçalves, Simon T Schafer, Fred H Gage
The dentate gyrus of the mammalian hippocampus continuously generates new neurons during adulthood. These adult-born neurons become functionally active and are thought to contribute to learning and memory, especially during their maturation phase, when they have extraordinary plasticity. In this Review, we discuss the molecular machinery involved in the generation of new neurons from a pool of adult neural stem cells and their integration into functional hippocampal circuits. We also summarize the potential functions of these newborn neurons in the adult brain, their contribution to behavior, and their relevance to disease...
November 3, 2016: Cell
https://www.readbyqxmd.com/read/27812545/low-dose-il-2-selectively-activates-subsets-of-cd4-tregs-and-nk-cells
#10
Masahiro Hirakawa, Tiago Matos, Hongye Liu, John Koreth, Haesook T Kim, Nicole E Paul, Kazuyuki Murase, Jennifer Whangbo, Ana C Alho, Sarah Nikiforow, Corey Cutler, Vincent T Ho, Philippe Armand, Edwin P Alyea, Joseph H Antin, Bruce R Blazar, Joao F Lacerda, Robert J Soiffer, Jerome Ritz
CD4(+) regulatory T cells (CD4Tregs) play a critical role in the maintenance of immune tolerance and prevention of chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation. IL-2 supports the proliferation and survival of CD4Tregs and previous studies have demonstrated that IL-2 induces selective expansion of CD4Tregs and improves clinical manifestations of chronic GVHD. However, mechanisms for selective activation of CD4Tregs and the effects of low-dose IL-2 on other immune cells are not well understood...
November 3, 2016: JCI Insight
https://www.readbyqxmd.com/read/27787795/differentiation-of-diverse-progenies-of-memory-t-cells-from-na%C3%A3-ve-cd8-t-cell-precursors
#11
Veronica Zanon, Enrico Lugli
Following recognition of the cognate antigen, naïve T cells differentiate in a diverse progeny of memory T cells which differ at the phenotypic, gene expression and metabolic level. These molecular differences are at the basis of discrete functionality, migratory capacity and persistence in the long-term. Such a division of labor benefits adoptive T cell transfer immunotherapy approaches for cancer and viral infections, as increased persistence and effector functions in vivo result in better control of the disease...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27760761/mva-vaccine-encoding-cmv-antigens-safely-induces-durable-expansion-of-cmv-specific-t-cells-in-healthy-adults
#12
Corinna La Rosa, Jeff Longmate, Joy Martinez, Qiao Zhou, Teodora I Kaltcheva, Weimin Tsai, Jennifer Drake, Mary Carroll, Felix Wussow, Flavia Chiuppesi, Nicola Hardwick, Sanjeet Dadwal, Ibrahim Aldoss, Ryotaro Nakamura, John A Zaia, Don J Diamond
Attenuated poxvirus Modified vaccinia Ankara (MVA) is a useful viral-based vaccine for clinical investigation, because of its excellent safety profile and property of inducing potent immune responses against recombinant (r) antigens. We developed Triplex by constructing an rMVA encoding three immunodominant CMV antigens which stimulates a host anti-viral response: UL83 (pp65), UL123 (IE1-exon4), and UL122 (IE2-exon5). We completed the first clinical evaluation of the Triplex vaccine in 24 healthy adults, with or without immunity to CMV and vaccinia virus (previous DryVax smallpox vaccination)...
October 19, 2016: Blood
https://www.readbyqxmd.com/read/27717382/discovery-of-immunodominant-t-cell-epitopes-reveals-penton-protein-as-a-second-immunodominant-target-in-human-adenovirus-infection
#13
Sabine Tischer, René Geyeregger, Julian Kwoczek, Albert Heim, Constanca Figueiredo, Rainer Blasczyk, Britta Maecker-Kolhoff, Britta Eiz-Vesper
BACKGROUND: Human adenovirus (HAdV) infections remain a significant cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Efficient antiviral T-cell responses are necessary to clear infection, which is hampered by delayed immune reconstitution and medical immunosuppression after HSCT. Protective immunity may be conferred by adoptive transfer of HAdV-specific T cells. For identification of patients at risk and monitoring of treatment responses diligent assessment of anti-HAdV cellular immune responses is crucial...
October 7, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27699218/the-mek-inhibitor-trametinib-separates-murine-graft-versus-host-disease-from-graft-versus-tumor-effects
#14
Hidekazu Itamura, Takero Shindo, Isao Tawara, Yasushi Kubota, Ryusho Kariya, Seiji Okada, Krishna V Komanduri, Shinya Kimura
The efficacy of allogeneic hematopoietic stem cell transplantation for hematologic malignancies is limited by the difficulty in suppressing graft-versus-host disease (GVHD) without compromising graft-versus-tumor (GVT) effects. We previously showed that RAS/MEK/ERK signaling depends on memory differentiation in human T cells, which confers susceptibility to selective inhibition of naive T cells. Actually, antineoplastic MEK inhibitors selectively suppress alloreactive T cells, sparing virus-specific T cells in vitro...
July 7, 2016: JCI Insight
https://www.readbyqxmd.com/read/27662090/inheritable-silencing-of-endogenous-genes-by-hit-and-run-targeted-epigenetic-editing
#15
Angelo Amabile, Alessandro Migliara, Paola Capasso, Mauro Biffi, Davide Cittaro, Luigi Naldini, Angelo Lombardo
Gene silencing is instrumental to interrogate gene function and holds promise for therapeutic applications. Here, we repurpose the endogenous retroviruses' silencing machinery of embryonic stem cells to stably silence three highly expressed genes in somatic cells by epigenetics. This was achieved by transiently expressing combinations of engineered transcriptional repressors that bind to and synergize at the target locus to instruct repressive histone marks and de novo DNA methylation, thus ensuring long-term memory of the repressive epigenetic state...
September 22, 2016: Cell
https://www.readbyqxmd.com/read/27634043/the-microrna-mir-191-supports-t-cell-survival-following-common-%C3%AE-chain-signaling
#16
Erik Allen Lykken, Qi-Jing Li
To ensure lifelong immunocompetency, naïve and memory T cells must be adequately maintained in the peripheral lymphoid tissues. Homeostatic maintenance of T cells is controlled by tonic signaling through T cell antigen receptors and common γ chain cytokine receptors. In this study, we identify the highly expressed microRNA miR-191 as a key regulator of naïve, memory, and regulatory T cell homeostasis. Conditional deletion of miR-191 using LckCre resulted in preferential loss of peripheral CD4(+) regulatory T cells as well as naïve and memory CD8(+) T cells...
November 4, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27631893/heterogeneity-of-specific-cd4-and-cd8-t-cells-stimulated-by-cmv-pp65-and-ie1-antigens
#17
Elena Albiero, Eliana Amati, Elke Baumeister, Hermann Einsele, Götz U Grigoleit, Francesco Rodeghiero
Characterization of human cytomegalovirus-specific T cells (CMV-T) is of critical importance for their potential use in adoptive immunotherapy after allogeneic hematopoietic stem cell transplantation. Background frequencies of CMV-T in peripheral blood mononuclear cells (PBMCs) of CMV-seropositive healthy subjects are usually very low, hence the requirement for prolonged culture time and multiple stimulations to expand them. The evaluation of the end-culture specificity and composition has sometimes been neglected or difficult to assess in these settings...
November 2016: Journal of Immunotherapy
https://www.readbyqxmd.com/read/27622012/ipilimumab-reshapes-t-cell-memory-subsets-in-melanoma-patients-with-clinical-response
#18
Joana Felix, Jérome Lambert, Marie Roelens, Eve Maubec, Hélène Guermouche, Cécile Pages, Irina Sidina, Debora J Cordeiro, Guitta Maki, François Chasset, Raphaël Porcher, Martine Bagot, Anne Caignard, Antoine Toubert, Céleste Lebbé, Hélène Moins-Teisserenc
PURPOSE: Therapy targeting CTLA-4 immune checkpoint provides increased survival in patients with advanced melanoma. However, immunotherapy is frequently associated with delayed and heterogeneous clinical responses and it is important to identify prognostic immunological correlates of clinical endpoints. EXPERIMENTAL DESIGN: 77 patients with stage III/IV melanoma were treated with ipilimumab alone every 3 weeks, during 9 weeks. Blood samples were collected at the baseline and before each dose for in depth immune monitoring...
July 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27620200/self-reactivity-as-the-necessary-cost-of-maintaining-a-diverse-memory-t-cell-repertoire
#19
Nevil J Singh
The adaptive immune system is expected to protect the host from infectious agents and malignancies, while avoiding robust activation against self-peptides. However, T cells are notoriously inept at protection whenever the pathogen or tumor is persistent in the body for longer periods of time. While this has been thought of as an adaptation to limit the immunopathology from continued effector T-cell responses, it is also likely an extension of the T cell's intrinsic mechanisms which evolved to tolerate self-peptides...
October 2016: Pathogens and Disease
https://www.readbyqxmd.com/read/27617863/abc-transporters-and-nr4a1-identify-a-quiescent-subset-of-tissue-resident-memory-t-cells
#20
Chandra Sekhar Boddupalli, Shiny Nair, Simon M Gray, Heba N Nowyhed, Rakesh Verma, Joanna A Gibson, Clara Abraham, Deepak Narayan, Juan Vasquez, Catherine C Hedrick, Richard A Flavell, Kavita M Dhodapkar, Susan M Kaech, Madhav V Dhodapkar
Immune surveillance in tissues is mediated by a long-lived subset of tissue-resident memory T cells (Trm cells). A putative subset of tissue-resident long-lived stem cells is characterized by the ability to efflux Hoechst dyes and is referred to as side population (SP) cells. Here, we have characterized a subset of SP T cells (Tsp cells) that exhibit a quiescent (G0) phenotype in humans and mice. Human Trm cells in the gut and BM were enriched in Tsp cells that were predominantly in the G0 stage of the cell cycle...
October 3, 2016: Journal of Clinical Investigation
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