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

Cell Immunol. 1997 May 25;178(1):42-52. doi: 10.1006/cimm.1997.1125.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Division / drug effects
  • Cell Line
  • Computer Simulation
  • Drug Synergism
  • Endocytosis
  • Humans
  • Interleukin-2 / pharmacology*
  • Interleukin-4 / pharmacology*
  • Lymphocyte Activation / drug effects*
  • Models, Immunological*
  • Receptors, Interleukin-2 / physiology
  • T-Lymphocytes / drug effects*

Substances

  • Interleukin-2
  • Receptors, Interleukin-2
  • Interleukin-4