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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Veröffentlicht in:PLoS computational biology Jg. 10; H. 8; S. e1003752
Hauptverfasser: Textor, Johannes, Henrickson, Sarah E., Mandl, Judith N., von Andrian, Ulrich H., Westermann, Jürgen, de Boer, Rob J., Beltman, Joost B.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States Public Library of Science 01.08.2014
Public Library of Science (PLoS)
Schlagworte:
Animals
Biology and Life Sciences
Cell adhesion & migration
Cell Communication - immunology
Cell migration
Cell Movement - immunology
Cell research
Computational Biology
Experiments
Health aspects
Humans
Immune system
Infection control
Infections
Lymph nodes
Lymphocytes
Mice
Models, Immunological
Monte Carlo simulation
Random variables
Retention
Signal Transduction
Surveillance
T cells
T-Lymphocytes - immunology
Viral infections
ISSN:1553-7358, 1553-734X, 1553-7358
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Zusammenfassung: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.
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The authors have declared that no competing interests exist.
Conceived and designed the experiments: JT JBB RJdB UHvA SEH JW. Performed the experiments: JT JBB. Wrote the paper: JT JBB RJdB JW SEH UHvA JNM. Performed mathematical and computational modeling: JT JBB.
ISSN:1553-7358
1553-734X
1553-7358
DOI:10.1371/journal.pcbi.1003752