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Multiscale Modeling of the Early CD8 T-Cell Immune Response in Lymph Nodes: An Integrative Study

Sotiris Prokopiou 1, * Loic Barbarroux 1, 2, 3 Samuel Bernard 1, 2 Julien Mafille 4 Yann Leverrier 4 Christophe Arpin 4 Jacqueline Marvel 4 Olivier Gandrillon 5, 1 Fabien Crauste 1, 2 
* Corresponding author
1 DRACULA - Multi-scale modelling of cell dynamics : application to hematopoiesis
CGPhiMC - Centre de génétique et de physiologie moléculaire et cellulaire, Inria Grenoble - Rhône-Alpes, ICJ - Institut Camille Jordan [Villeurbanne]
3 MMCS - Modélisation mathématique, calcul scientifique
ICJ - Institut Camille Jordan [Villeurbanne]
4 Immunité et lymphocytes cytotoxiques – Immunity and cytotoxic lymphocytes
CIRI - Centre International de Recherche en Infectiologie - UMR
Abstract : CD8 T-cells are critical in controlling infection by intracellular pathogens. Upon encountering antigen presenting cells, T-cell receptor activation promotes the differentiation of naïve CD8 T-cells into strongly proliferating activated and effector stages. We propose a 2D-multiscale computational model to study the maturation of CD8 T-cells in a lymph node controlled by their molecular profile. A novel molecular pathway is presented and converted into an ordinary differential equation model, coupled with a cellular Potts model to describe cell-cell interactions. Key molecular players such as activated IL2 receptor and Tbet levels control the differentiation from naïve into activated and effector stages, respectively, while caspases and Fas-Fas ligand interactions control cell apoptosis. Coupling this molecular model to the cellular scale successfully reproduces qualitatively the evolution of total CD8 T-cell counts observed in mice lymph node, between Day 3 and 5.5 post-infection. Furthermore, this model allows us to make testable predictions of the evolution of the different CD8 T-cell stages.
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Contributor : Fabien Crauste Connect in order to contact the contributor
Submitted on : Wednesday, October 15, 2014 - 12:14:24 PM
Last modification on : Monday, May 16, 2022 - 3:12:02 PM

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Sotiris Prokopiou, Loic Barbarroux, Samuel Bernard, Julien Mafille, Yann Leverrier, et al.. Multiscale Modeling of the Early CD8 T-Cell Immune Response in Lymph Nodes: An Integrative Study. Computation, MDPI, 2014, 2 (4), pp.159-181. ⟨10.3390/computation2040159⟩. ⟨hal-01074736⟩



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