Modeling and characterization of inter-individual variability in CD8 T cell responses in mice.
In Silico Biol
; 14(1-2): 13-39, 2021.
Article
em En
| MEDLINE
| ID: mdl-33554899
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Contexto em Saúde:
2_ODS3
/
4_TD
Problema de saúde:
2_enfermedades_transmissibles
/
4_smallpox
Assunto principal:
Vaccinia virus
/
Linfócitos T CD8-Positivos
Limite:
Animals
Idioma:
En
Revista:
In Silico Biol
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
França