Human TSCM cell dynamics in vivo are compatible with long-lived immunological memory and stemness.
Adaptive immunity relies on the generation and maintenance of memory T cells to provide protection against repeated antigen exposure. It has been hypothesised that a self-renewing population of T cells, named stem cell-like memory T (TSCM) cells, are responsible for maintaining memory. However, it i...
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doaj-c85bfaa7e2db4200835697b9df1f03c92021-07-02T03:59:57ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852018-06-01166e200552310.1371/journal.pbio.2005523Human TSCM cell dynamics in vivo are compatible with long-lived immunological memory and stemness.Pedro Costa Del AmoJulio Lahoz-BeneytezLies BoelenRaya AhmedKelly L MinersYan ZhangLaureline RogerRhiannon E JonesSilvia A Fuertes MarracoDaniel E SpeiserDuncan M BairdDavid A PriceKristin LadellDerek MacallanBecca AsquithAdaptive immunity relies on the generation and maintenance of memory T cells to provide protection against repeated antigen exposure. It has been hypothesised that a self-renewing population of T cells, named stem cell-like memory T (TSCM) cells, are responsible for maintaining memory. However, it is not clear if the dynamics of TSCM cells in vivo are compatible with this hypothesis. To address this issue, we investigated the dynamics of TSCM cells under physiological conditions in humans in vivo using a multidisciplinary approach that combines mathematical modelling, stable isotope labelling, telomere length analysis, and cross-sectional data from vaccine recipients. We show that, unexpectedly, the average longevity of a TSCM clone is very short (half-life < 1 year, degree of self-renewal = 430 days): far too short to constitute a stem cell population. However, we also find that the TSCM population is comprised of at least 2 kinetically distinct subpopulations that turn over at different rates. Whilst one subpopulation is rapidly replaced (half-life = 5 months) and explains the rapid average turnover of the bulk TSCM population, the half-life of the other TSCM subpopulation is approximately 9 years, consistent with the longevity of the recall response. We also show that this latter population exhibited a high degree of self-renewal, with a cell residing without dying or differentiating for 15% of our lifetime. Finally, although small, the population was not subject to excessive stochasticity. We conclude that the majority of TSCM cells are not stem cell-like but that there is a subpopulation of TSCM cells whose dynamics are compatible with their putative role in the maintenance of T cell memory.http://europepmc.org/articles/PMC6033534?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Pedro Costa Del Amo Julio Lahoz-Beneytez Lies Boelen Raya Ahmed Kelly L Miners Yan Zhang Laureline Roger Rhiannon E Jones Silvia A Fuertes Marraco Daniel E Speiser Duncan M Baird David A Price Kristin Ladell Derek Macallan Becca Asquith |
spellingShingle |
Pedro Costa Del Amo Julio Lahoz-Beneytez Lies Boelen Raya Ahmed Kelly L Miners Yan Zhang Laureline Roger Rhiannon E Jones Silvia A Fuertes Marraco Daniel E Speiser Duncan M Baird David A Price Kristin Ladell Derek Macallan Becca Asquith Human TSCM cell dynamics in vivo are compatible with long-lived immunological memory and stemness. PLoS Biology |
author_facet |
Pedro Costa Del Amo Julio Lahoz-Beneytez Lies Boelen Raya Ahmed Kelly L Miners Yan Zhang Laureline Roger Rhiannon E Jones Silvia A Fuertes Marraco Daniel E Speiser Duncan M Baird David A Price Kristin Ladell Derek Macallan Becca Asquith |
author_sort |
Pedro Costa Del Amo |
title |
Human TSCM cell dynamics in vivo are compatible with long-lived immunological memory and stemness. |
title_short |
Human TSCM cell dynamics in vivo are compatible with long-lived immunological memory and stemness. |
title_full |
Human TSCM cell dynamics in vivo are compatible with long-lived immunological memory and stemness. |
title_fullStr |
Human TSCM cell dynamics in vivo are compatible with long-lived immunological memory and stemness. |
title_full_unstemmed |
Human TSCM cell dynamics in vivo are compatible with long-lived immunological memory and stemness. |
title_sort |
human tscm cell dynamics in vivo are compatible with long-lived immunological memory and stemness. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Biology |
issn |
1544-9173 1545-7885 |
publishDate |
2018-06-01 |
description |
Adaptive immunity relies on the generation and maintenance of memory T cells to provide protection against repeated antigen exposure. It has been hypothesised that a self-renewing population of T cells, named stem cell-like memory T (TSCM) cells, are responsible for maintaining memory. However, it is not clear if the dynamics of TSCM cells in vivo are compatible with this hypothesis. To address this issue, we investigated the dynamics of TSCM cells under physiological conditions in humans in vivo using a multidisciplinary approach that combines mathematical modelling, stable isotope labelling, telomere length analysis, and cross-sectional data from vaccine recipients. We show that, unexpectedly, the average longevity of a TSCM clone is very short (half-life < 1 year, degree of self-renewal = 430 days): far too short to constitute a stem cell population. However, we also find that the TSCM population is comprised of at least 2 kinetically distinct subpopulations that turn over at different rates. Whilst one subpopulation is rapidly replaced (half-life = 5 months) and explains the rapid average turnover of the bulk TSCM population, the half-life of the other TSCM subpopulation is approximately 9 years, consistent with the longevity of the recall response. We also show that this latter population exhibited a high degree of self-renewal, with a cell residing without dying or differentiating for 15% of our lifetime. Finally, although small, the population was not subject to excessive stochasticity. We conclude that the majority of TSCM cells are not stem cell-like but that there is a subpopulation of TSCM cells whose dynamics are compatible with their putative role in the maintenance of T cell memory. |
url |
http://europepmc.org/articles/PMC6033534?pdf=render |
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