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Spatial Lymphocyte Dynamics in Lymph Nodes Predicts the Cytotoxic T Cell Frequency Needed for HIV Infection Control.

Title: Spatial Lymphocyte Dynamics in Lymph Nodes Predicts the Cytotoxic T Cell Frequency Needed for HIV Infection Control.
Authors: Grebennikov D; Moscow Institute of Physics and Technology, National Research University, Dolgoprudny, Russia.; Marchuk Institute of Numerical Mathematics, Russian Academy of Sciences, Moscow, Russia.; Peoples' Friendship University of Russia (RUDN University), Moscow, Russia.; Bouchnita A; Division of Scientific Computing, Department of Information Technology, Uppsala University, Uppsala, Sweden.; Volpert V; Peoples' Friendship University of Russia (RUDN University), Moscow, Russia.; Institut Camille Jordan, UMR 5208 CNRS, University Lyon 1, Villeurbanne, France.; INRIA Team Dracula, INRIA Lyon La Doua, Villeurbanne, France.; Bessonov N; Institute of Problems of Mechanical Engineering, Russian Academy of Sciences, Saint Petersburg, Russia.; Meyerhans A; Infection Biology Laboratory, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.; Bocharov G; Marchuk Institute of Numerical Mathematics, Russian Academy of Sciences, Moscow, Russia.; Sechenov First Moscow State Medical University, Moscow, Russia.
Source: Frontiers in immunology [Front Immunol] 2019 Jun 11; Vol. 10, pp. 1213. Date of Electronic Publication: 2019 Jun 11 (Print Publication: 2019).
Publication Type: Journal Article; Research Support, Non-U.S. Gov't
Language: English
Journal Info: Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE
Imprint Name(s): Original Publication: [Lausanne : Frontiers Research Foundation]
MeSH Terms: Models, Immunological*; CD4-Positive T-Lymphocytes/*immunology ; HIV Infections/*immunology ; HIV-1/*immunology ; Lymph Nodes/*immunology ; T-Lymphocytes, Cytotoxic/*immunology; CD4-Positive T-Lymphocytes/pathology ; HIV Infections/pathology ; Lymph Nodes/pathology ; T-Lymphocytes, Cytotoxic/pathology ; Humans
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.
Comments: Erratum in: Front Immunol. 2019 Jul 03;10:1538. doi: 10.3389/fimmu.2019.01538.. (PMID: 31333669)
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Contributed Indexing: Keywords: HIV infection; cell motility; cytotoxic T cell scanning; dissipative particle dynamics; lymphoid tissue; multicellular dynamics; stochastic differential equation
Entry Date(s): Date Created: 20190628 Date Completed: 20201029 Latest Revision: 20201029
Update Code: 20260130
PubMed Central ID: PMC6579925
DOI: 10.3389/fimmu.2019.01213
PMID: 31244829
Database: MEDLINE

Journal Article; Research Support, Non-U.S. Gov't