Modeling the proliferative response of T cells to IL-2 and IL-4

Cellular Immunology
M A BurkeP A Morel

Abstract

Interleukin (IL) -2 and IL-4 are growth factors for both T and B cells. When both cytokines are present, synergy is observed in some cases and antagonism in others. The studies presented here describe the use of a detailed mathematical model for the proliferative response of the T cell line, HT-2. This cell line responds to IL-2 and to IL-4 and shows a synergistic response when both cytokines are present. This model incorporates the observed synergy between these two cytokines while at the same time incorporating the known down-regulatory effect of IL-4 on the number of IL-2 receptors (IL-2R) at the cell surface, and it is able to reproduce a variety of experimental data. The major results from these studies include the following: the observation that the binding of IL-4 to its receptor is 1/10 as effective in delivering a proliferative signal as IL-2 binding to its receptor, the determination of the threshold number of bindings required to signal proliferation stimulated by IL-2 and IL-4, the demonstration that many different sets of experimental data can be accurately modeled, and the use of simple parameter terms to model the synergy between IL-2 and IL-4.

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Citations

Aug 27, 2014·Journal of Pharmacokinetics and Pharmacodynamics·Penelope A MorelNatasa Miskov-Zivanov
Sep 1, 2008·Cellular and Molecular Bioengineering·Kristen K Comfort, Jason M Haugh
May 8, 2010·Brain, Behavior, and Immunity·Gordon BroderickMary Ann Fletcher
Oct 1, 2007·Drug Discovery Today. Disease Models·Silvia Daun, Gilles Clermont
Sep 26, 2003·Scandinavian Journal of Immunology·L ForchhammerM H Claesson
Jun 30, 2007·Oral Microbiology and Immunology·J F ManakilP M Bartold
Oct 3, 2000·Journal of Theoretical Biology·A YatesR Callard
Jun 7, 2017·American Journal of Reproductive Immunology : AJRI·Adi L TarcaRoberto Romero
Aug 22, 2018·Immunological Reviews·Joseph M CiccheseDenise E Kirschner
Feb 13, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·J E Wigginton, D Kirschner

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