title: Random migration and signal integration promote rapid and robust T cell recruitment.
abstract: 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.
authors.affiliation: Theoretical Biology & Bioinformatics, Utrecht University, Utrecht, The Netherlands.
authors.forename: Johannes
authors.initials: J
authors.lastname: Textor
authors.affiliation: Department of Pathology, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Henrickson
authors.affiliation: Lymphocyte Biology Section, National Insitutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Judith N
authors.initials: JN
authors.lastname: Mandl
authors.affiliation: Department of Pathology, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Ulrich H
authors.initials: UH
authors.lastname: von Andrian
authors.affiliation: Institute for Anatomy, University of Lübeck, Lübeck, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Westermann
authors.affiliation: Theoretical Biology & Bioinformatics, Utrecht University, Utrecht, The Netherlands.
authors.forename: Rob J
authors.initials: RJ
authors.lastname: de Boer
authors.affiliation: Theoretical Biology & Bioinformatics, Utrecht University, Utrecht, The Netherlands; Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Joost B
authors.initials: JB
authors.lastname: Beltman
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology*; D019295:Computational Biology; D006801:Humans; D051379:Mice; D018448:Models, Immunological; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
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