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

Publication date: 13 December 2016
Source:Cell Reports, Volume 17, Issue 11
Author(s): 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. 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.

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Teaser

Stem cell-like memory T (TSCM) cells are multipotent progenitors that can both self-renew and replenish more differentiated subsets of memory T cells. Ahmed et al. find that human TSCM cells are maintained by ongoing proliferation and display limited telomere length erosion coupled with high expression levels of active telomerase and Ki67.


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