3 years ago

Regulatory T Cells Suppress Effector T Cell Proliferation by Limiting Division Destiny.

Mark R. Dowling, Andrey Kan, Susanne Heinzel, Julia M. Marchingo, Philip D. Hodgkin, Edwin D. Hawkins
Understanding how the strength of an effector T cell response is regulated is a fundamental problem in immunology with implications for immunity to pathogens, autoimmunity, and immunotherapy. The initial magnitude of the T cell response is determined by the sum of independent signals from antigen, co-stimulation and cytokines. By applying quantitative methods, the contribution of each signal to the number of divisions T cells undergo (division destiny) can be measured, and the resultant exponential increase in response magnitude accurately calculated. CD4+CD25+Foxp3+ regulatory T cells suppress self-reactive T cell responses and limit pathogen-directed immune responses before bystander damage occurs. Using a quantitative modeling framework to measure T cell signal integration and response, we show that Tregs modulate division destiny, rather than directly increasing the rate of death or delaying interdivision times. The quantitative effect of Tregs could be mimicked by modulating the availability of stimulatory co-stimuli and cytokines or through the addition of inhibitory signals. Thus, our analysis illustrates the primary effect of Tregs on the magnitude of effector T cell responses is mediated by modifying division destiny of responding cell populations.

Publisher URL: http://doi.org/10.3389/fimmu.2018.02461

Open URL: https://doi.org/10.3389/fimmu.2018.02461

DOI: 10.3389/fimmu.2018.02461

Open access
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