Modeling and characterization of inter-individual variability in CD8 T cell responses in mice

Chloe Audebert; Daphné Laubreton; Christophe Arpin; Olivier Gandrillon; Jacqueline Marvel; Fabien Crauste

doi:10.3233/isb-200205

journal article Open Access May 28, 2021

Modeling and characterization of inter-individual variability in CD8 T cell responses in mice

Chloe Audebert Daphné Laubreton

Christophe Arpin Olivier Gandrillon

Jacqueline Marvel

Fabien Crauste

In Silico Biology: Journal of Biological Systems Modeling and Multi-Scale Simulation Vol. 14 No. 1-2 pp. 13-39 · SAGE Publications

View at Publisher Save 10.3233/isb-200205

Abstract

To develop vaccines it is mandatory yet challenging to account for inter-individual variability during immune responses. Even in laboratory mice, T cell responses of single individuals exhibit a high heterogeneity that may come from genetic backgrounds, intra-specific processes (e.g. antigen-processing and presentation) and immunization protocols. To account for inter-individual variability in CD8 T cell responses in mice, we propose a dynamical model coupled to a statistical, nonlinear mixed effects model. Average and individual dynamics during a CD8 T cell response are characterized in different immunization contexts (vaccinia virus and tumor). On one hand, we identify biological processes that generate inter-individual variability (activation rate of naive cells, the mortality rate of effector cells, and dynamics of the immunogen). On the other hand, introducing categorical covariates to analyze two different immunization regimens, we highlight the steps of the response impacted by immunogens (priming, differentiation of naive cells, expansion of effector cells and generation of memory cells). The robustness of the model is assessed by confrontation to new experimental data. Our approach allows to investigate immune responses in various immunization contexts, when measurements are scarce or missing, and contributes to a better understanding of inter-individual variability in CD8 T cell immune responses.

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Details

Published: May 28, 2021
Vol/Issue: 14(1-2)
Pages: 13-39
License: View

Authors

C

Chloe Audebert

Inria Dracula, Villeurbanne, France; Sorbonne Université, CNRS, Université de Paris, Laboratoire Jacques-Louis Lions UMR 7598, F-75005 Paris, France; Sorbonne Université, CNRS, Institut de biologie Paris-Seine (IBPS), Laboratoire de Biologie Computationnelle et Quantitative UMR 7238, F-75005 Paris, France

D

Daphné Laubreton

Centre International de recherche en Infectiologie, Université de Lyon, INSERM U1111, CNRS UMR 5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard Lyon 1, 69007 Lyon, France

C

Christophe Arpin

Centre International de recherche en Infectiologie, Université de Lyon, INSERM U1111, CNRS UMR 5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard Lyon 1, 69007 Lyon, France

O

Olivier Gandrillon

Inria Dracula, Villeurbanne, France; Laboratory of Biology and Modelling of the Cell, Université de Lyon, ENS de Lyon, Université Claude Bernard, CNRS UMR 5239, INSERM U1210, 69007 Lyon, France

J

Jacqueline Marvel

Centre International de recherche en Infectiologie, Université de Lyon, INSERM U1111, CNRS UMR 5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard Lyon 1, 69007 Lyon, France

F

Fabien Crauste

Inria Dracula, Villeurbanne, France; Université de Paris, MAP5, CNRS, F-75006, France

Cite This Article

Chloe Audebert, Daphné Laubreton, Christophe Arpin, et al. (2021). Modeling and characterization of inter-individual variability in CD8 T cell responses in mice. In Silico Biology: Journal of Biological Systems Modeling and Multi-Scale Simulation, 14(1-2), 13-39. https://doi.org/10.3233/isb-200205

Modeling and characterization of inter-individual variability in CD8 T cell responses in mice

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