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Memory Stem T-Cells

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https://www.readbyqxmd.com/read/28060797/t-memory-stem-cells-in-health-and-disease
#1
REVIEW
Luca Gattinoni, Daniel E Speiser, Mathias Lichterfeld, Chiara Bonini
T memory stem (TSCM) cells are a rare subset of memory lymphocytes endowed with the stem cell-like ability to self-renew and the multipotent capacity to reconstitute the entire spectrum of memory and effector T cell subsets. Cumulative evidence in mice, nonhuman primates and humans indicates that TSCM cells are minimally differentiated cells at the apex of the hierarchical system of memory T lymphocytes. Here we describe emerging findings demonstrating that TSCM cells, owing to their extreme longevity and robust potential for immune reconstitution, are central players in many physiological and pathological human processes...
January 6, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28057064/the-lncrnas-involved-in-mouse-airway-allergic-inflammation-following-induced-pluripotent-stem-cell-mesenchymal-stem-cell-treatment
#2
Shu-Yue Wang, Xing-Liang Fan, Qiu-Ning Yu, Meng-Xia Deng, Yue-Qi Sun, Wen-Xiang Gao, Cheng-Lin Li, Jian-Bo Shi, Qing-Ling Fu
BACKGROUND: We have previously reported that induced pluripotent stem cell (iPSC)-mesenchymal stem cells (MSCs) alleviated asthma inflammation in mice. Long noncoding RNAs (lncRNAs) were recently reported as being involved in the immune responses. However, whether lncRNAs are associated with iPSC-MSC immunomodulation in allergic inflammation is still unclear. METHODS: Mice were induced into an asthmatic state and received treatment consisting of iPSC-MSCs. Memory T cells isolated from sensitized mice were challenged and co-cultured with iPSC-MSCs in vitro...
January 6, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28034872/fetal-and-adult-progenitors-give-rise-to-unique-populations-of-cd8-t-cells
#3
Jocelyn Wang, Erin M Wissink, Neva B Watson, Norah L Smith, Andrew Grimson, Brian D Rudd
During the ontogeny of the mammalian immune system, distinct lineages of cells arise from fetal and adult hematopoietic stem cells (HSCs) during specific stages of development. However, in some cases, the same immune cell type is produced by both HSC populations, resulting in the generation of phenotypically similar cells with distinct origins and divergent functional properties. In this report, we demonstrate that neonatal CD8(+) T cells preferentially become short-lived effectors and adult CD8(+) T cells selectively form long-lived memory cells after infection because they are derived from distinct progenitor cells...
December 29, 2016: Blood
https://www.readbyqxmd.com/read/28027219/cancer-risk-after-fat-transfer-a-multicenter-case-cohort-study
#4
Terence M Myckatyn, I Janelle Wagner, Babak J Mehrara, Melissa A Crosby, Julie E Park, Bahjat F Qaqish, Dominic T Moore, Evan L Busch, Amanda K Silva, Surinder Kaur, David W Ollila, Clara N Lee
BACKGROUND: Fat transfer is an increasingly popular method for refining postmastectomy breast reconstructions. However, concern persists that fat transfer may promote disease recurrence. Adipocytes are derived from adipose-derived stem cells and express adipocytokines that can facilitate active breast cancer cells in laboratory models. The authors sought to evaluate the association between fat transfer to the reconstructed breast and cancer recurrence in patients diagnosed with local or regional invasive breast cancers...
January 2017: Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/28018990/the-tcf1-bcl6-axis-counteracts-type-i-interferon-to-repress-exhaustion-and-maintain-t-cell-stemness
#5
Tuoqi Wu, Yun Ji, E Ashley Moseman, Haifeng C Xu, Monica Manglani, Martha Kirby, Stacie M Anderson, Robin Handon, Elizabeth Kenyon, Abdel Elkahloun, Weiwei Wu, Philipp A Lang, Luca Gattinoni, Dorian B McGavern, Pamela L Schwartzberg
During chronic viral infections and in cancer, T cells become dysfunctional, a state known as T cell exhaustion. Although it is well recognized that memory CD8 T cells account for the persistence of CD8 T cell immunity after acute infection, how exhausted T cells persist remains less clear. Using chronic infection with lymphocytic choriomeningitis virus clone 13 and tumor samples, we demonstrate that CD8 T cells differentiate into a less exhausted TCF1(high) and a more exhausted TCF1(low) population. Virus-specific TCF1(high) CD8 T cells, which resemble T follicular helper (TFH) cells, persist and recall better than do TCF1(low) cells and act as progenitor cells to replenish TCF1(low) cells...
December 23, 2016: Science Immunology
https://www.readbyqxmd.com/read/27998208/increasing-stem-cell-dose-promotes-posttransplant-immune-reconstitution
#6
Ning Xu, Sylvie Shen, Alla Dolnikov
Umbilical cord blood (UCB) transplantation can provide a successful therapeutic option for patients that have no suitable related donor. UCB transplantation is often limited by the relatively small hematopoietic stem cell (HSC) numbers in UCB especially for adult recipients. Early neutrophil and platelet engraftment correlates with the stem cell numbers in UCB transplant. Compared to other HSC sources, immune reconstitution following UCB transplant is slower and complicated by increased frequency of opportunistic infections...
January 16, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/27997758/comprehensive-mass-cytometry-analysis-of-cell-cycle-activation-and-co-inhibitory-receptors-expression-in-cd4-t-cells-from-healthy-and-hiv-infected-individuals
#7
REVIEW
Aurélien Corneau, Antonio Cosma, Sophie Even, Christine Katlama, Roger Legrand, Véronique Frachet, Catherine Blanc, Brigitte Autran
RATIONALE: Mass cytometry allows large multiplex analysis of cell cycle stages together with differentiation, activation and exhaustion markers, allowing further assessment of the quiescence status of resting CD4 T cells. METHODS: peripheral blood CD4 T lymphocytes from 8 individuals, 4 healthy donors (HD) and 4 HIV-infected on anti-retroviral treatment (T) were stained with the same 26 monoclonal antibodies and dyes targeting surface and intra-cellular markers of differentiation, activation, exhaustion and cell cycle stages...
December 20, 2016: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/27974195/human-stem-cell-like-memory-t-cells-are-maintained-in-a-state-of-dynamic-flux
#8
Raya Ahmed, Laureline Roger, Pedro Costa Del Amo, Kelly L Miners, Rhiannon E Jones, Lies Boelen, Tinhinane Fali, Marjet Elemans, Yan Zhang, Victor Appay, Duncan M Baird, Becca Asquith, David A Price, Derek C Macallan, Kristin Ladell
Adaptive immunity requires the generation of memory T cells from naive precursors selected in the thymus. The key intermediaries in this process are stem cell-like memory T (TSCM) cells, multipotent progenitors that can both self-renew and replenish more differentiated subsets of memory T cells. In theory, antigen specificity within the TSCM pool may be imprinted statically as a function of largely dormant cells and/or retained dynamically by more transitory subpopulations. To explore the origins of immunological memory, we measured the turnover of TSCM cells in vivo using stable isotope labeling with heavy water...
December 13, 2016: Cell Reports
https://www.readbyqxmd.com/read/27943115/harnessing-bone-marrow-resident-regulatory-t-cells-to-improve-allogeneic-stem-cell-transplant-outcomes
#9
REVIEW
Laetitia Le Texier, Katie E Lineburg, Kelli P A MacDonald
Regulatory T cells (Treg) are a suppressive T cell population which play a crucial role in the establishment of tolerance after stem cell transplantation (SCT) by controlling the effector T cell responses that drive acute and chronic GVHD. The BM compartment is enriched in a highly suppressive, activated/memory autophagy-dependent Treg population, which contributes to the HSC engraftment and the control of GVHD. G-CSF administration releases Treg from the BM through disruption of the CXCR4/SDF-1 axis and further improves Treg survival following SCT through the induction of autophagy...
December 10, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27942862/altered-immune-reconstitution-of-b-and-t-cells-precedes-the-onset-of-clinical-symptoms-of-chronic-graft-versus-host-disease-and-is-influenced-by-the-type-of-onset
#10
E-M Bohmann, U Fehn, B Holler, D Weber, E Holler, W Herr, P Hoffmann, M Edinger, D Wolff
We analyzed lymphocyte subpopulations and cytokines 3 months after allogeneic hematopoietic stem cell transplantation aiming to identify predictive cellular and serum markers for chronic graft-versus-host disease (cGVHD). Samples of 49 patients (pts) (no cGVHD (n = 14), subsequent quiescent onset (n = 16), de novo onset of cGVHD (n = 19)) were analyzed in the absence of active GVHD by flow cytometry and enzyme-linked immunosorbent assay. All mean absolute cell counts are presented as cells per microliter; relative cell counts are presented as percentage of lymphocytes...
December 9, 2016: Annals of Hematology
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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...
February 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27814520/adult-neurogenesis-in-the-hippocampus-from-stem-cells-to-behavior
#19
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
#20
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
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