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

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 computation...

Full description

Bibliographic Details
Main Authors: Sotiris A. Prokopiou, Loic Barbarroux, Samuel Bernard, Julien Mafille, Yann Leverrier, Christophe Arpin, Jacqueline Marvel, Olivier Gandrillon, Fabien Crauste
Format: Article
Language:English
Published: MDPI AG 2014-09-01
Series:Computation
Subjects:
Online Access:http://www.mdpi.com/2079-3197/2/4/159
Description
Summary: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.
ISSN:2079-3197