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

Sotiris Prokopiou; Loic Barbarroux; Samuel Bernard; Julien Mafille; Yann Leverrier; Christophe Arpin; Jacqueline Marvel; Olivier Gandrillon; Fabien Crauste

doi:10.3390/computation2040159

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 ⁴ Julien Mafille ⁵ Yann Leverrier ⁵ Christophe Arpin ⁵ Jacqueline Marvel ^{6, 5} Olivier Gandrillon ^{7, 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]

2 ICJ - Institut Camille Jordan [Villeurbanne]

3 MMCS - Modélisation mathématique, calcul scientifique

ICJ - Institut Camille Jordan [Villeurbanne]

4 UCBL - Université Claude Bernard Lyon 1

5 Immunité et lymphocytes cytotoxiques – Immunity and cytotoxic lymphocytes

CIRI - Centre International de Recherche en Infectiologie - UMR

6 SFR Biosciences

7 CGPhiMC - Centre de génétique et de physiologie moléculaire et cellulaire

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.

Keywords : cellular Potts model CD8 T-cells APC multiscale immune modeling

Document type :

Journal articles

Domain :

Computer Science [cs] / Modeling and Simulation

Life Sciences [q-bio] / Immunology

Life Sciences [q-bio] / Quantitative Methods [q-bio.QM]

Liste complète des métadonnées

https://hal.inria.fr/hal-01074736
Contributor : Fabien Crauste <>
Submitted on : Wednesday, October 15, 2014 - 12:14:24 PM
Last modification on : Friday, April 12, 2019 - 10:40:03 AM

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

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

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