Arias, Clemente F.Herrero García, Miguel ÁngelCuesta, José A.Acosta Salmerón, Francisco JavierFernández Arias, Cristina2024-01-292024-01-292015-07-08Arias CF, Herrero MA, Cuesta JA, Acosta FJ, Fernández-Arias C. The growth threshold conjecture: a theoretical framework for understanding T-cell tolerance. R Soc Open Sci. 2015 Jul 8;2(7):150016. doi: 10.1098/rsos.150016. PMID: 26587263; PMCID: PMC4632576.2054-570310.1098/rsos.150016https://hdl.handle.net/20.500.14352/96049Adaptive 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.engAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/journal articlehttps://royalsocietypublishing.org/doi/10.1098/rsos.150016https://pubmed.ncbi.nlm.nih.gov/26587263/open access612.017T cellsimmune selfimmune toleranceimmunodominancenegative selectionCiencias Biomédicas24 Ciencias de la Vida2412 Inmunología