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A multiscale model of the CD8 T cell immune response structured by intracellular content

Loic Barbarroux 1, 2, 3, 4 Philippe Michel 2, 3, 4 Mostafa Adimy 1, 3, 4 Fabien Crauste 1, 3, 4
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]
4 MMCS - Modélisation mathématique, calcul scientifique
ICJ - Institut Camille Jordan [Villeurbanne]
Abstract : During the primary CD8 T cell immune response, CD8 T cells undergo proliferation and continuous differentiation, acquiring cytotoxic abilities to address the infection and generate an immune memory. At the end of the response, the remaining CD8 T cells are antigen-specific memory cells that will respond stronger and faster in case they are presented this very same antigen again. We propose a nonlinear multiscale mathematical model of the CD8 T cell immune response describing dynamics of two inter-connected physical scales. At the intracellular scale, the level of expression of key proteins involved in proliferation, death, and differentiation of CD8 T cells is modeled by a delay differential system whose dynamics define maturation velocities of CD8 T cells. At the population scale, the amount of CD8 T cells is represented by a discrete density and cell fate depends on their intracellular content. We introduce the model, then show essential mathematical properties (existence, uniqueness, positivity) of solutions and analyse their asymptotic behavior based on the behavior of the intracellular regulatory network. We numerically illustrate the model's ability to qualitatively reproduce both primary and secondary responses, providing a preliminary tool for investigating the generation of long-lived CD8 memory T cells and vaccine design.
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Contributor : Mostafa Adimy <>
Submitted on : Thursday, January 17, 2019 - 9:55:09 AM
Last modification on : Monday, June 28, 2021 - 2:26:07 PM

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Loic Barbarroux, Philippe Michel, Mostafa Adimy, Fabien Crauste. A multiscale model of the CD8 T cell immune response structured by intracellular content. Discrete and Continuous Dynamical Systems - Series B, American Institute of Mathematical Sciences, 2018, 23 (9), pp.3969-4002. ⟨10.3934/dcdsb.2018120⟩. ⟨hal-01969237⟩



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