Original Research ARTICLE
Fate of a naive T cell: a stochastic journey
- 1University of Leeds, United Kingdom
- 2Comillas Pontifical University, Spain
- 3University College London, United Kingdom
The homeostasis of different T cell sub-populations depends on migration, division and death of individual cells. T cells migrate between spatial compartments (e.g., blood, spleen, lymph nodes, lung, liver, etc.), divide or differentiate during their stay in these compartments, and eventually die. The kinetics of this recirculation influences the speed at which local infections are detected and controlled (1). New experimental techniques have been developed to measure the lifespan of cells, and their migration dynamics; for example, fluorescence-activated cell sorting (2), in vitro time-lapse microscopy (3), or in vivo stable isotope labelling (e.g., deuterium) (4). When combined with mathematical and computational models, they allow estimation of rates of migration, division, differentiation and death (5). In this work, we consider a stochastic model of a single cell migrating between spatial compartments, dividing and eventually dying. We calculate the number of division events during a T cell’s journey, its lifespan, the probability of dying in each compartment and the number of progeny cells. A rapid-migration approximation allows us to compute these quantities when migration rates are much higher than division and death rates. Making use of published rates: (i) we analyse how perturbations in a given spatial compartment impact T cell dynamics, (ii) we study the accuracy of the rapid-migration approximation, and (iii) we quantify the role played by direct migration (not via the blood) between some compartments.
Keywords: T cell, stochastic, Continuous Time Markov Chain (CTMC), single cell, cellular fate, Migration, proliferation, Apoptosis
Received: 28 Jun 2018;
Accepted: 23 Jan 2019.
Edited by:Jorge Bernardino De La Serna, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, United Kingdom
Reviewed by:RUIAN KE, Los Alamos National Laboratory (DOE), United States
M J Lopez-Herrero, Complutense University of Madrid, Spain
María Teresa R. Bernal, Facultad de Ciencias Matematicas, Universidad Complutense de Madrid, Spain
Copyright: © 2019 de la Higuera, Lopez-Garcia, Castro, Abourashchi, Lythe and Molina-Paris. 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.
* Correspondence: Dr. Martin Lopez-Garcia, University of Leeds, Leeds, LS2 9JT, United Kingdom, firstname.lastname@example.org