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Human stem cell-like memory T cells are maintained in a state of dynamic flux

Ahmed, Raya, Roger, Laureline, Costa del Amo, Pedro, Miners, Kelly L., Jones, Rhiannon E., Boelen, Lies, Fali, Tinhinane, Elemans, Marjet, Zhang, Yan, Appay, Victor, Baird, Duncan M., Asquith, Becca, Price, David A., Macallan, Derek C. and Ladell, Kristin 2016. Human stem cell-like memory T cells are maintained in a state of dynamic flux. Cell Reports 17 (11) , pp. 2811-2818. 10.1016/j.celrep.2016.11.037

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Publisher: Elsevier
ISSN: 2211-1247
Funders: Wellcome Trust, MRC, CRUK
Date of First Compliant Deposit: 14 December 2016
Date of Acceptance: 10 November 2016
Last Modified: 12 May 2020 12:00

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