The growth threshold conjecture: a theoretical framework for understanding T-cell tolerance.
The growth threshold conjecture: a theoretical framework for understanding T-cell tolerance.
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DOI：
10.1098/rsos.150016
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发表时间：
2015-07
影响因子：
3.5
通讯作者：
Fernández-Arias C
中科院分区：
文献类型：
--
作者：
Arias CF;Herrero MA;Cuesta JA;Acosta FJ;Fernández-Arias C
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.
