Human TSCM cell dynamics in vivo are compatible with long-lived immunological memory and stemness.

Details

Serval ID
serval:BIB_D04E45903CAD
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Human TSCM cell dynamics in vivo are compatible with long-lived immunological memory and stemness.
Journal
PLoS biology
Author(s)
Costa Del Amo P., Lahoz-Beneytez J., Boelen L., Ahmed R., Miners K.L., Zhang Y., Roger L., Jones R.E., Marraco SAF, Speiser D.E., Baird D.M., Price D.A., Ladell K., Macallan D., Asquith B.
ISSN
1545-7885 (Electronic)
ISSN-L
1544-9173
Publication state
Published
Issued date
06/2018
Peer-reviewed
Oui
Volume
16
Number
6
Pages
e2005523
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
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.
Keywords
Adult, Aged, 80 and over, CD4-Positive T-Lymphocytes/cytology, CD4-Positive T-Lymphocytes/immunology, CD8-Positive T-Lymphocytes/cytology, CD8-Positive T-Lymphocytes/immunology, Cell Self Renewal/immunology, Humans, Immunologic Memory, Kinetics, Mathematical Concepts, Middle Aged, Models, Immunological, T-Lymphocyte Subsets/cytology, T-Lymphocyte Subsets/immunology, Telomere Homeostasis/immunology, Yellow fever virus/immunology
Pubmed
Web of science
Open Access
Yes
Create date
29/06/2018 16:51
Last modification date
20/08/2019 15:50
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