Modeling the proliferative response of T cells to IL-2 and IL-4.
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.
Burke
M A
MA
Department of Medicine, University of Pittsburgh, Pennsylvania 15260, USA.
Morel
B F
BF
Oriss
T B
TB
Bray
J
J
McCarthy
S A
SA
Morel
P A
PA
D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003198:Computer Simulation; D004357:Drug Synergism; D004705:Endocytosis; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D018448:Models, Immunological; D015375:Receptors, Interleukin-2 / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects*
D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D015847:Interleukin-4