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The Rules of Human T Cell Fate in vivo.

Costa Del Amo, P; Debebe, B; Razavi-Mohseni, M; Nakaoka, S; Worth, A; Wallace, D; Beverley, P; Macallan, D; Asquith, B (2020) The Rules of Human T Cell Fate in vivo. Front Immunol, 11. p. 573. ISSN 1664-3224 https://doi.org/10.3389/fimmu.2020.00573
SGUL Authors: Macallan, Derek Clive

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Abstract

The processes governing lymphocyte fate (division, differentiation, and death), are typically assumed to be independent of cell age. This assumption has been challenged by a series of elegant studies which clearly show that, for murine cells in vitro, lymphocyte fate is age-dependent and that younger cells (i.e., cells which have recently divided) are less likely to divide or die. Here we investigate whether the same rules determine human T cell fate in vivo. We combined data from in vivo stable isotope labeling in healthy humans with stochastic, agent-based mathematical modeling. We show firstly that the choice of model paradigm has a large impact on parameter estimates obtained using stable isotope labeling i.e., different models fitted to the same data can yield very different estimates of T cell lifespan. Secondly, we found no evidence in humans in vivo to support the model in which younger T cells are less likely to divide or die. This age-dependent model never provided the best description of isotope labeling; this was true for naïve and memory, CD4+ and CD8+ T cells. Furthermore, this age-dependent model also failed to predict an independent data set in which the link between division and death was explored using Annexin V and deuterated glucose. In contrast, the age-independent model provided the best description of both naïve and memory T cell dynamics and was also able to predict the independent dataset.

Item Type: Article
Additional Information: Copyright © 2020 Costa del Amo, Debebe, Razavi-Mohseni, Nakaoka, Worth, Wallace, Beverley, Macallan and Asquith. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Keywords: decision, fate, half-life, labeling, lifespan, lymphocyte, mathematical model, proliferation
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: Front Immunol
ISSN: 1664-3224
Language: eng
Dates:
DateEvent
8 April 2020Published
12 March 2020Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
103865Wellcome Trusthttp://dx.doi.org/10.13039/100004440
317040Seventh Framework Programmehttp://dx.doi.org/10.13039/501100004963
J007439Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
G1001052Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
15012Leukemia and Lymphoma ResearchUNSPECIFIED
JPMJPR16E9JST PRESTO programUNSPECIFIED
25871132Japan Society for the Promotion of Sciencehttp://dx.doi.org/10.13039/501100001691
16K052565Japan Society for the Promotion of Sciencehttp://dx.doi.org/10.13039/501100001691
PubMed ID: 32322253
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/111916
Publisher's version: https://doi.org/10.3389/fimmu.2020.00573

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