Human Stem Cell-like Memory T Cells Are Maintained in a State of Dynamic Flux.


Author: Ahmed R1, Roger L2, Costa Del Amo P3, Miners KL2, Jones RE4, Boelen L3, Fali T5, Elemans M3, Zhang Y1, Appay V5, Baird DM4, Asquith B3, Price DA6, Macallan DC7, Ladell K8

Affiliation: <sup>1</sup>Institute for Infection and Immunity, St. George's, University of London, London SW17 0RE, UK.

<sup>2</sup>Division of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.

<sup>3</sup>Department of Medicine, St. Mary's Hospital, Imperial College London, London W2 1PG, UK.

<sup>4</sup>Division of Cancer and Genetics, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.

<sup>5</sup>Sorbonne Universités, UPMC Université Paris 06, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 75013 Paris, France; INSERM U1135, CIMI-Paris, 75013 Paris, France.

<sup>6</sup>Division of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: priced6@cardiff.ac.uk.

<sup>7</sup>Institute for Infection and Immunity, St. George's, University of London, London SW17 0RE, UK; St. George's University Hospitals National Health Service Foundation Trust, Blackshaw Road, London SW17 0QT, UK. Electronic address: macallan@sgul.ac.uk.

<sup>8</sup>Division of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK. Electronic address: ladellk@gmail.com.
Conference/Journal: Cell Rep.
Date published: 2016 Dec 13
Other:
 Volume ID: 17   ,  Issue ID: 11   ,  Pages: 2811-2818   ,  Special Notes: doi: 10.1016/j.celrep.2016.11.037.   ,  Word Count: 196  
    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. The data indicate that TSCM cells in both young and elderly subjects are maintained by ongoing proliferation. In line with this finding, TSCM cells displayed limited telomere length erosion coupled with high expression levels of active telomerase and Ki67. Collectively, these observations show that TSCM cells exist in a state of perpetual flux throughout the human lifespan.



Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.



KEYWORDS: CD4(+) T cells; CD8(+) T cells; adaptive immunity; in vivo heavy water labeling; memory T cell maintenance; memory T cells; proliferation; stem cell-like memory T cells; telomerase activity; telomere length



PMID: 27974195  DOI: 10.1016/j.celrep.2016.11.037