Terry Emmanuelle, Marvel Jacqueline, Arpin Christophe, Gandrillon Olivier, Crauste Fabien
Université de Lyon, Université Lyon 1, CNRS UMR 5208, Institut Camille Jordan, 43 blvd du 11 novembre 1918, 69622, Villeurbanne-Cedex, France.
J Math Biol. 2012 Aug;65(2):263-91. doi: 10.1007/s00285-011-0459-8. Epub 2011 Aug 13.
The primary CD8 T cell immune response, due to a first encounter with a pathogen, happens in two phases: an expansion phase, with a fast increase of T cell count, followed by a contraction phase. This contraction phase is followed by the generation of memory cells. These latter are specific of the antigen and will allow a faster and stronger response when encountering the antigen for the second time. We propose a nonlinear mathematical model describing the T CD8 immune response to a primary infection, based on three nonlinear ordinary differential equations and one nonlinear age-structured partial differential equation, describing the evolution of CD8 T cell count and pathogen amount. We discuss in particular the roles and relevance of feedback controls that regulate the response. First we reduce our system to a system with a nonlinear differential equation with a distributed delay. We study the existence of two steady states, and we analyze the asymptotic stability of these steady states. Second we study the system with a discrete delay, and analyze global asymptotic stability of steady states. Finally, we show some simulations that we can obtain from the model and confront them to experimental data.
由于首次接触病原体,初始CD8 T细胞免疫反应分两个阶段发生:一个是扩增阶段,T细胞数量快速增加,随后是收缩阶段。收缩阶段之后是记忆细胞的产生。这些记忆细胞是抗原特异性的,当第二次遇到抗原时会产生更快更强的反应。我们提出了一个非线性数学模型,基于三个非线性常微分方程和一个非线性年龄结构偏微分方程,描述CD8 T细胞免疫反应对初次感染的响应,该模型描述了CD8 T细胞数量和病原体数量的演变。我们特别讨论了调节该反应的反馈控制的作用和相关性。首先,我们将系统简化为一个具有分布延迟的非线性微分方程系统。我们研究了两个稳态的存在性,并分析了这些稳态的渐近稳定性。其次,我们研究了具有离散延迟的系统,并分析了稳态的全局渐近稳定性。最后,我们展示了从该模型获得的一些模拟结果,并将它们与实验数据进行对比。