%0 Journal Article
%A Arias, Clemente F.
%A Herrero García, Miguel Ángel
%A Cuesta, José A.
%A Acosta Salmerón, Francisco Javier
%A Fernández Arias, Cristina
%T The growth thresh- old conjecture: a theoretical framework for understanding T-cell tolerance
%D 2015
%@ 2054-5703
%U https://hdl.handle.net/20.500.14352/96049
%X 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.
%~