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Article

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

1
Inria team Dracula, Inria center Grenoble Rhone-Alpes, 66 Boulevard Niels Bohr,-69603, France
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Université Lyon 1, CNRS UMR 5208, Institut Camille Jordan, 43 blvd du 11 novembre 1918, F-69622 Villeurbanne-Cedex, France
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Inserm, U1111, Lyon F-69007, France
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CNRS, UMR5308, Lyon F-69007, France
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Université Lyon 1, Centre International de Recherche en Infectiologie, Lyon F-69007, France
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Ecole Normale Supérieure de Lyon, Lyon F-69007, France
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Université Lyon 1, Centre de Génétique et de Physiologie Moléculaire et Cellulaire, F-69622 Villeurbanne-Cedex, France
*
Author to whom correspondence should be addressed.
Received: 28 May 2014 / Revised: 18 July 2014 / Accepted: 4 September 2014 / Published: 29 September 2014
(This article belongs to the Special Issue Computational Studies of Immune System Function)
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. View Full-Text
Keywords: multiscale immune modeling; cellular Potts model; CD8 T-cells; APC multiscale immune modeling; cellular Potts model; CD8 T-cells; APC
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MDPI and ACS Style

Prokopiou, S.A.; Barbarroux, L.; Bernard, S.; Mafille, J.; Leverrier, Y.; Arpin, C.; Marvel, J.; Gandrillon, O.; Crauste, F. Multiscale Modeling of the Early CD8 T-Cell Immune Response in Lymph Nodes: An Integrative Study. Computation 2014, 2, 159-181. https://0-doi-org.brum.beds.ac.uk/10.3390/computation2040159

AMA Style

Prokopiou SA, Barbarroux L, Bernard S, Mafille J, Leverrier Y, Arpin C, Marvel J, Gandrillon O, Crauste F. Multiscale Modeling of the Early CD8 T-Cell Immune Response in Lymph Nodes: An Integrative Study. Computation. 2014; 2(4):159-181. https://0-doi-org.brum.beds.ac.uk/10.3390/computation2040159

Chicago/Turabian Style

Prokopiou, Sotiris A., Loic Barbarroux, Samuel Bernard, Julien Mafille, Yann Leverrier, Christophe Arpin, Jacqueline Marvel, Olivier Gandrillon, and Fabien Crauste. 2014. "Multiscale Modeling of the Early CD8 T-Cell Immune Response in Lymph Nodes: An Integrative Study" Computation 2, no. 4: 159-181. https://0-doi-org.brum.beds.ac.uk/10.3390/computation2040159

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