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Functional Switching and Stability of Regulatory T Cells

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Abstract

It is widely accepted that the primary immune system contains a subpopulation of cells, known as regulatory T cells whose function is to regulate the immune response. There is conflicting biological evidence regarding the ability of regulatory cells to lose their regulatory capabilities and turn into immune promoting cells. In this paper, we develop mathematical models to investigate the effects of regulatory T cell switching on the immune response. Depending on environmental conditions, regulatory T cells may transition, becoming effector T cells that are immunostimulatory rather than immunoregulatory. We consider this mechanism both in the context of a simple, ordinary differential equation (ODE) model and in the context of a more biologically detailed, delay differential equation (DDE) model of the primary immune response. It is shown that models that incorporate such a mechanism express the usual characteristics of an immune response (expansion, contraction, and memory phases), while being more robust with respect to T cell precursor frequencies. We characterize the affects of regulatory T cell switching on the peak magnitude of the immune response and identify a biologically testable range for the switching parameter. We conclude that regulatory T cell switching may play a key role in controlling immune contraction.

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Acknowledgements

We would like to thank Peter Kim for sharing his code. This work was supported in part by the joint NSF/NIGMS program under Grant Number DMS-0758374 and in part by Grant Number R01CA130817 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.

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  1. NUMED Team, Inovallée, INRIA, 655 avenue de l’Europe, 38330, Montbonnot-Saint-Martin, France

    Shelby Wilson

  2. Department of Mathematics and Center for Scientific Computation and Mathematical Modeling (CSCAMM), University of Maryland, College Park, MD, 20742, USA

    Doron Levy

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Correspondence to Doron Levy.

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Wilson, S., Levy, D. Functional Switching and Stability of Regulatory T Cells. Bull Math Biol 75, 1891–1911 (2013). https://doi.org/10.1007/s11538-013-9875-9

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  • DOI: https://doi.org/10.1007/s11538-013-9875-9

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