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Computation 2014, 2(4), 159-181; doi:10.3390/computation2040159

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
2
Université Lyon 1, CNRS UMR 5208, Institut Camille Jordan, 43 blvd du 11 novembre 1918, F-69622 Villeurbanne-Cedex, France
3
Inserm, U1111, Lyon F-69007, France
4
CNRS, UMR5308, Lyon F-69007, France
5
Université Lyon 1, Centre International de Recherche en Infectiologie, Lyon F-69007, France
6
Ecole Normale Supérieure de Lyon, Lyon F-69007, France
7
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)
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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. View Full-Text
Keywords: multiscale immune modeling; cellular Potts model; CD8 T-cells; APC multiscale immune modeling; cellular Potts model; CD8 T-cells; APC
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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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.

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