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The growth threshold conjecture: a theoretical framework for understanding T-cell tolerance

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Arias, Clemente F. and Herrero, Miguel A. and Cuesta, José A. and Acosta Salmerón, Francisco Javier and Fernández Arias, Cristina (2015) The growth threshold conjecture: a theoretical framework for understanding T-cell tolerance. Royal Society Open Science, 2 (7). pp. 1-15. ISSN ESSN: 2054-5703

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Official URL: https://royalsocietypublishing.org/doi/10.1098/rsos.150016



Abstract

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.


Item Type:Article
Uncontrolled Keywords:T cells; Immune tolerance; Negative selection; Immunodominance; Immune self
Subjects:Medical sciences > Medicine > Immunology
Medical sciences > Biology > Molecular biology
Medical sciences > Biology > Biomathematics
ID Code:55039
Deposited On:12 Apr 2019 11:04
Last Modified:12 Apr 2019 11:30

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