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

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 proli...

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Detalles Bibliográficos
Autores: Arias, Clemente F., Herrero García, Miguel Ángel, Cuesta, José A., Acosta Salmerón, Francisco Javier, Fernández Arias, Cristina
Tipo de recurso: artículo
Fecha de publicación:2015
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/96049
Acceso en línea:https://hdl.handle.net/20.500.14352/96049
Access Level:acceso abierto
Palabra clave:612.017
T cells
immune self
immune tolerance
immunodominance
negative selection
Ciencias Biomédicas
24 Ciencias de la Vida
2412 Inmunología
Descripción
Sumario: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.