Imperial College London
Alternate

Dr Becca Asquith

Faculty of Medicine, Department of Infectious Disease

Professor of Mathematical Immunology
 
 
 
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Contact

 

+44 (0)20 7594 3731b.asquith

 
 
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Location

 

112Wright Fleming WingSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Costa:2018:10.1371/journal.pbio.2005523,
author = {Costa, del Amo P and Lahoz-Beneytez, J and Boelen, L and Ahmed, R and Miners, KL and Zhang, Y and Roger, L and Jones, RE and Fuertes, Marraco SA and Speiser, DE and Baird, DM and Price, DA and Ladell, K and Macallan, D and Asquith, B},
doi = {10.1371/journal.pbio.2005523},
journal = {PLoS Biology},
title = {Human TSCM cell dynamics in vivo are compatible with long-lived immunological memory and stemness},
url = {http://dx.doi.org/10.1371/journal.pbio.2005523},
volume = {16},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Costa,del Amo P
AU  - Lahoz-Beneytez,J
AU  - Boelen,L
AU  - Ahmed,R
AU  - Miners,KL
AU  - Zhang,Y
AU  - Roger,L
AU  - Jones,RE
AU  - Fuertes,Marraco SA
AU  - Speiser,DE
AU  - Baird,DM
AU  - Price,DA
AU  - Ladell,K
AU  - Macallan,D
AU  - Asquith,B
DO  - 10.1371/journal.pbio.2005523
PY  - 2018///
SN  - 1544-9173
TI  - Human TSCM cell dynamics in vivo are compatible with long-lived immunological memory and stemness
T2  - PLoS Biology
UR  - http://dx.doi.org/10.1371/journal.pbio.2005523
UR  - http://hdl.handle.net/10044/1/61465
VL  - 16
ER  -
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