Spatial lymphocyte dynamics in lymph nodes predicts the cytotoxic T cell frequency needed for HIV infection control

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• dc.contributor.author Grebennikov, Dmitry
• dc.contributor.author Bouchnita, Anass
• dc.contributor.author Volpert, Vitaly
• dc.contributor.author Bessonov, Nickolay
• dc.contributor.author Meyerhans, Andreas
• dc.contributor.author Bocharov, Gennady A.
• dc.date.accessioned 2019-07-01T10:36:25Z
• dc.date.available 2019-07-01T10:36:25Z
• dc.date.issued 2019
• dc.description.abstract The surveillance of host body tissues by immune cells is central for mediating their defense function. In vivo imaging technologies have been used to quantitatively characterize target cell scanning and migration of lymphocytes within lymph nodes (LNs). The translation of these quantitative insights into a predictive understanding of immune system functioning in response to various perturbations critically depends on computational tools linking the individual immune cell properties with the emergent behavior of the immune system. By choosing the Newtonian second law for the governing equations, we developed a broadly applicable mathematical model linking individual and coordinated T-cell behaviors. The spatial cell dynamics is described by a superposition of autonomous locomotion, intercellular interaction, and viscous damping processes. The model is calibrated using in vivo data on T-cell motility metrics in LNs such as the translational speeds, turning angle speeds, and meandering indices. The model is applied to predict the impact of T-cell motility on protection against HIV infection, i.e., to estimate the threshold frequency of HIV-specific cytotoxic T cells (CTLs) that is required to detect productively infected cells before the release of viral particles starts. With this, it provides guidance for HIV vaccine studies allowing for the migration of cells in fibrotic LNs.
• dc.description.sponsorship This work is supported by the Russian Science Foundation (grant 18-11-00171). VV was supported by a grant from the RUDN University Program 5-100. AM is also supported by a grant from the Spanish Ministry of Economy, Industry and Competitiveness and FEDER grant no. SAF2016-75505-R (AEI/MINEICO/FEDER, UE) and the María de Maeztu Programme for Units of Excellence in R&D (MDM-2014-0370).
• dc.format.mimetype application/pdf
• dc.identifier.citation Grebennikov D, Bouchnita A, Volpert V, Bessonov N, Meyerhans A, Bocharov G. Spatial lymphocyte dynamics in lymph nodes predicts the cytotoxic T cell frequency needed for HIV infection control. Front Immunol. 2019;10:1213. DOI: 10.3389/fimmu.2019.01213
• dc.identifier.doi http://dx.doi.org/10.3389/fimmu.2019.01213
• dc.identifier.issn 1664-3224
• dc.identifier.uri http://hdl.handle.net/10230/41900
• dc.language.iso eng
• dc.publisher Frontiers
• dc.relation.ispartof Frontiers in Immunology. 2019; 10:1213
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2016-75505-R
• dc.rights © 2019 Grebennikov, Bouchnita, Volpert, Bessonov, Meyerhans and Bocharov. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (http://creativecommons.org/licenses/by/4.0/). 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.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Lymphoid tissue
• dc.subject.keyword Cell motility
• dc.subject.keyword HIV infection
• dc.subject.keyword Cytotoxic T cell scanning
• dc.subject.keyword Multicellular dynamics
• dc.subject.keyword Dissipative particle dynamics
• dc.subject.keyword Stochastic differential equation
• dc.title Spatial lymphocyte dynamics in lymph nodes predicts the cytotoxic T cell frequency needed for HIV infection control
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion