Imperial College London
Alternate

Dr Becca Asquith

Faculty of Medicine, Department of Infectious Disease

Professor of Mathematical Immunology
 
 
 
//

Contact

 

+44 (0)20 7594 3731b.asquith

 
 
//

Location

 

112Wright Fleming WingSt Mary's Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Costa:2020:10.3389/fimmu.2020.00573,
author = {Costa, Del Amo P and Debebe, B and Razavi-Mohseni, M and Nakaoka, S and Worth, A and Wallace, D and Beverley, P and Macallan, D and Asquith, B},
doi = {10.3389/fimmu.2020.00573},
journal = {Frontiers in Immunology},
title = {The rules of human T cell fate in vivo},
url = {http://dx.doi.org/10.3389/fimmu.2020.00573},
volume = {11},
year = {2020}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Costa,Del Amo P
AU  - Debebe,B
AU  - Razavi-Mohseni,M
AU  - Nakaoka,S
AU  - Worth,A
AU  - Wallace,D
AU  - Beverley,P
AU  - Macallan,D
AU  - Asquith,B
DO  - 10.3389/fimmu.2020.00573
PY  - 2020///
SN  - 1664-3224
TI  - The rules of human T cell fate in vivo
T2  - Frontiers in Immunology
UR  - http://dx.doi.org/10.3389/fimmu.2020.00573
UR  - http://hdl.handle.net/10044/1/78853
VL  - 11
ER  -
Download