Mathematical modeling reveals the biological program regulating lymphopenia-induced proliferation.

The Journal of Immunology : Official Journal of the American Association of Immunologists
Andrew YatesBenedict Seddon

Abstract

Recognition of peptide-MHC by the TCR induces T lymphocytes to undergo cell division. Although recognition of foreign peptide induces a program of cellular division and differentiation by responding T cells, stimulation by self-peptide MHC complexes in lymphopenic conditions induces a slower burst of divisions that may or may not be accompanied by effector differentiation. Although both responses are triggered by signals from the TCR, it is not known whether they represent distinct programs of cell cycle control. In this study, we use a mathematical modeling approach to analyze the proliferative response of TCR transgenic F5 T cells to lymphopenia. We tested two fundamentally different models of cell division: one in which T cells are triggered into an "autopilot" deterministic burst of divisions, a model successfully used elsewhere to describe T cell responses to cognate Ag, and a second contrasting model in which cells undergo independent single stochastic divisions. Whereas the autopilot model provided a very poor description of the F5 T cell responses to lymphopenia, the model of single stochastic divisions fitted the experimental data remarkably closely. Furthermore, this model proved robust because specific predictions of...Continue Reading

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Citations

Oct 5, 2012·Journal of the Royal Society, Interface·Vitaly V Ganusov, Rob J De Boer
Mar 12, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Thea HoganBenedict Seddon
Aug 6, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ina Schim van der LoeffBenedict Seddon
Nov 27, 2015·Proceedings of the National Academy of Sciences of the United States of America·Thea HoganBenedict Seddon
Aug 19, 2015·Mathematical Biosciences and Engineering : MBE·Houssein AyoubRodolphe Thiebaut
Jan 12, 2017·Clinical Pharmacology and Therapeutics·R L HoareJ F Standing
Aug 2, 2020·The FEBS Journal·Darina Paprckova, Ondrej Stepanek
Aug 22, 2018·Immunological Reviews·Benedict Seddon, Andrew J Yates
Nov 23, 2020·Biochemical and Biophysical Research Communications·Bahire KalfaogluMasahiro Ono

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