AUTHOR=de la Higuera Luis , López-García Martín , Castro Mario , Abourashchi Niloufar , Lythe Grant , Molina-París Carmen 

TITLE=Fate of a Naive T Cell: A Stochastic Journey

JOURNAL=Frontiers in Immunology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.00194

DOI=10.3389/fimmu.2019.00194

ISSN=1664-3224

ABSTRACT=<p>The homeostasis of T cell populations depends on migration, division and death of individual cells (<xref ref-type="bibr" rid="B1">1</xref>). T cells migrate between spatial compartments (spleen, lymph nodes, lung, liver, etc.), where they may divide or differentiate, and eventually die (<xref ref-type="bibr" rid="B2">2</xref>). The kinetics of recirculation influences the speed at which local infections are detected and controlled (<xref ref-type="bibr" rid="B3">3</xref>). New experimental techniques have been developed to measure the lifespan of cells, and their migration dynamics; for example, fluorescence-activated cell sorting (<xref ref-type="bibr" rid="B4">4</xref>), <italic>in vitro</italic> time-lapse microscopy (<xref ref-type="bibr" rid="B5">5</xref>), or <italic>in vivo</italic> stable isotope labeling (e.g., deuterium) (<xref ref-type="bibr" rid="B6">6</xref>). When combined with mathematical and computational models, they allow estimation of rates of migration, division, differentiation and death (<xref ref-type="bibr" rid="B6">6</xref>, <xref ref-type="bibr" rid="B7">7</xref>). In this work, we develop 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 fast-migration approximation allows us to compute these quantities when migration rates are larger than division and death rates. Making use of published rates: (i) we analyse how perturbations in a given spatial compartment impact the dynamics of a T cell, (ii) we study the accuracy of the fast-migration approximation, and (iii) we quantify the role played by direct migration (not via the blood) between some compartments.</p>