Random migration and signal integration promote rapid and robust T cell recruitment.

To fight infections, rare T cells must quickly home to appropriate lymph nodes (LNs), and reliably localize the antigen (Ag) within them. The first challenge calls for rapid trafficking between LNs, whereas the second may require extensive search within each LN. Here we combine simulations and exper...

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Autores principales:	Johannes Textor, Sarah E Henrickson, Judith N Mandl, Ulrich H von Andrian, Jürgen Westermann, Rob J de Boer, Joost B Beltman
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/229a5459e6ff4cffa93b60e78b6ac2b6
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spelling	oai:doaj.org-article:229a5459e6ff4cffa93b60e78b6ac2b62021-11-25T05:40:52ZRandom migration and signal integration promote rapid and robust T cell recruitment.1553-734X1553-735810.1371/journal.pcbi.1003752https://doaj.org/article/229a5459e6ff4cffa93b60e78b6ac2b62014-08-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25102014/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358To fight infections, rare T cells must quickly home to appropriate lymph nodes (LNs), and reliably localize the antigen (Ag) within them. The first challenge calls for rapid trafficking between LNs, whereas the second may require extensive search within each LN. Here we combine simulations and experimental data to investigate which features of random T cell migration within and between LNs allow meeting these two conflicting demands. Our model indicates that integrating signals from multiple random encounters with Ag-presenting cells permits reliable detection of even low-dose Ag, and predicts a kinetic feature of cognate T cell arrest in LNs that we confirm using intravital two-photon data. Furthermore, we obtain the most reliable retention if T cells transit through LNs stochastically, which may explain the long and widely distributed LN dwell times observed in vivo. Finally, we demonstrate that random migration, both between and within LNs, allows recruiting the majority of cognate precursors within a few days for various realistic infection scenarios. Thus, the combination of two-scale stochastic migration and signal integration is an efficient and robust strategy for T cell immune surveillance.Johannes TextorSarah E HenricksonJudith N MandlUlrich H von AndrianJürgen WestermannRob J de BoerJoost B BeltmanPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 10, Iss 8, p e1003752 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Johannes Textor Sarah E Henrickson Judith N Mandl Ulrich H von Andrian Jürgen Westermann Rob J de Boer Joost B Beltman Random migration and signal integration promote rapid and robust T cell recruitment.
description	To fight infections, rare T cells must quickly home to appropriate lymph nodes (LNs), and reliably localize the antigen (Ag) within them. The first challenge calls for rapid trafficking between LNs, whereas the second may require extensive search within each LN. Here we combine simulations and experimental data to investigate which features of random T cell migration within and between LNs allow meeting these two conflicting demands. Our model indicates that integrating signals from multiple random encounters with Ag-presenting cells permits reliable detection of even low-dose Ag, and predicts a kinetic feature of cognate T cell arrest in LNs that we confirm using intravital two-photon data. Furthermore, we obtain the most reliable retention if T cells transit through LNs stochastically, which may explain the long and widely distributed LN dwell times observed in vivo. Finally, we demonstrate that random migration, both between and within LNs, allows recruiting the majority of cognate precursors within a few days for various realistic infection scenarios. Thus, the combination of two-scale stochastic migration and signal integration is an efficient and robust strategy for T cell immune surveillance.
format	article
author	Johannes Textor Sarah E Henrickson Judith N Mandl Ulrich H von Andrian Jürgen Westermann Rob J de Boer Joost B Beltman
author_facet	Johannes Textor Sarah E Henrickson Judith N Mandl Ulrich H von Andrian Jürgen Westermann Rob J de Boer Joost B Beltman
author_sort	Johannes Textor
title	Random migration and signal integration promote rapid and robust T cell recruitment.
title_short	Random migration and signal integration promote rapid and robust T cell recruitment.
title_full	Random migration and signal integration promote rapid and robust T cell recruitment.
title_fullStr	Random migration and signal integration promote rapid and robust T cell recruitment.
title_full_unstemmed	Random migration and signal integration promote rapid and robust T cell recruitment.
title_sort	random migration and signal integration promote rapid and robust t cell recruitment.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/229a5459e6ff4cffa93b60e78b6ac2b6
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Random migration and signal integration promote rapid and robust T cell recruitment.

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