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

publication date

  • July 2015

issue

  • 2

Electronic International Standard Serial Number (EISSN)

  • 2054-5703

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.

keywords

  • negative selection; T cells; immune self; immunodominance; immune tolerance