Departamento de Matemática Aplicada, and , Universidad Complutense de Madrid , Madrid, Spain ; Departamento de Ecología , Universidad Complutense de Madrid , Madrid, Spain.
Departamento de Matemática Aplicada, and , Universidad Complutense de Madrid , Madrid, Spain.
R Soc Open Sci. 2015 Jul 8;2(7):150016. doi: 10.1098/rsos.150016. eCollection 2015 Jul.
Adaptive immune responses depend on the capacity of T cells to target specific antigens. As similar antigens can be expressed by pathogens and host cells, the question naturally arises of how can T cells discriminate friends from foes. In this work, we suggest that T cells tolerate cells whose proliferation rates remain below a permitted threshold. Our proposal relies on well-established facts about T-cell dynamics during acute infections: T-cell populations are elastic (they expand and contract) and they display inertia (contraction is delayed relative to antigen removal). By modelling inertia and elasticity, we show that tolerance to slow-growing populations can emerge as a population-scale feature of T cells. This result suggests a theoretical framework to understand immune tolerance that goes beyond the self versus non-self dichotomy. It also accounts for currently unexplained observations, such as the paradoxical tolerance to slow-growing pathogens or the presence of self-reactive T cells in the organism.
适应性免疫反应依赖于 T 细胞靶向特定抗原的能力。由于相似的抗原可以由病原体和宿主细胞表达，因此自然而然地会出现这样的问题：T 细胞如何区分敌我。在这项工作中，我们提出 T 细胞耐受其增殖率保持在允许阈值以下的细胞。我们的建议依赖于急性感染期间 T 细胞动力学的既定事实：T 细胞群体具有弹性（它们扩张和收缩）并且表现出惯性（收缩相对于抗原去除而延迟）。通过对惯性和弹性进行建模，我们表明，对生长缓慢的群体的耐受性可以作为 T 细胞的群体特征出现。这一结果为理解免疫耐受提供了一个理论框架，超越了自我与非我二分法。它还解释了目前尚无法解释的观察结果，例如对生长缓慢的病原体的悖论性耐受或机体中存在自身反应性 T 细胞。
