Arias Clemente F, Herrero Miguel A, Acosta Francisco J, Fernandez-Arias Cristina
Departamento de Ecología, Universidad Complutense de Madrid, Avda. Complutense s/n, Madrid 28040, Spain.
Departamento de Matemática Aplicada, Universidad Complutense de Madrid, Plaza de Ciencias 3, Madrid 28040, Spain.
J Theor Biol. 2014 May 21;349:109-20. doi: 10.1016/j.jtbi.2014.01.039. Epub 2014 Feb 8.
We formulate and analyze an algorithm of cell fate decision that describes the way in which division vs. apoptosis choices are made by individual T cells during an infection. Such model involves a minimal number of known biochemical mechanisms: it basically relies on the interplay between cell division and cell death inhibitors on one hand, and membrane receptors on the other. In spite of its simplicity, the proposed decision algorithm is able to account for some significant facts in immune response. At the individual level, the existence of T cells that continue to replicate in the absence of antigen and the possible occurrence of T cell apoptosis in the presence of antigen are predicted by the model. Moreover, the latter is shown to yield an emergent collective behavior, the observed delay in clonal contraction with respect to the end of antigen stimulation, which is shown to arise just from individual T cell decisions made according to the proposed mechanism.
我们制定并分析了一种细胞命运决定算法，该算法描述了在感染期间单个T细胞做出分裂与凋亡选择的方式。这种模型涉及最少数量的已知生化机制：它基本上一方面依赖于细胞分裂和细胞死亡抑制剂之间的相互作用，另一方面依赖于膜受体。尽管该算法很简单，但所提出的决策算法能够解释免疫反应中的一些重要事实。在个体层面，模型预测了在没有抗原的情况下继续复制的T细胞的存在以及在有抗原的情况下T细胞可能发生的凋亡。此外，后者显示出产生一种涌现的集体行为，即观察到的克隆收缩相对于抗原刺激结束的延迟，结果表明这种延迟仅源于根据所提出的机制做出的单个T细胞决策。
