title: The growth threshold conjecture: a theoretical framework for understanding T-cell tolerance.
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.
authors.affiliation: Departamento de Matemática Aplicada, and , Universidad Complutense de Madrid , Madrid, Spain ; Departamento de Ecología , Universidad Complutense de Madrid , Madrid, Spain.
authors.forename: Clemente F
authors.initials: CF
authors.lastname: Arias
authors.affiliation: Departamento de Matemática Aplicada, and , Universidad Complutense de Madrid , Madrid, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Herrero
authors.affiliation: Grupo Interdisciplinar de Sistemas Complejos , Madrid, Spain ; Departamento de Matemáticas , Universidad Carlos III de Madrid , Leganés, Madrid, Spain ; Instituto de Biocomputación y Física de Sistemas Complejos (BIFI) , Universidad de Zaragoza , Zaragoza, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Cuesta
authors.affiliation: Departamento de Ecología , Universidad Complutense de Madrid , Madrid, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Acosta
authors.affiliation: Department of Microbiology, Division of Parasitology , New York University School of Medicine , New York, NY, USA.
authors.forename: Cristina
authors.initials: C
authors.lastname: Fernández-Arias
keywords: T cells; immune self; immune tolerance; immunodominance; negative selection