A mathematical model of T lymphocyte proliferation controlled by interleukin-2 internalization.
A mathematical model of the first in vitro IL-2-controlled division cycle of T lymphocytes is presented. The model describes the population dynamics of T cells at different stages of the cell cycle and introduces "molecular" equations for the G1-S phase control. These equations are based on the current knowledge of the biochemical mechanisms of ligand-receptor binding, ligand and receptor synthesis, and internalization of the ligand-receptor complexes. The temporal order in the biosynthesis of IL-2 and IL-2R during the G1a and G1b phases is investigated. We show numerically that the maximum number of cells in the S-phase depends on the reversibility of the G1a-G1b transitions, on the rates of ligand-receptor binding, ligand and receptor synthesis, and internalization of the ligand-receptor complexes. The phase portraits for different hypotheses on the temporal order of the IL-2 and high affinity receptor synthesis at the G1 phase of the cell cycle are qualitatively different. On this basis, simple kinetic experiments to distinguish between these alternatives are proposed.
Borisova
L R
LR
Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Moscow.
Kuznetsov
V A
VA
D000818:Animals; D004705:Endocytosis; D016193:G1 Phase / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology* / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008962:Models, Theoretical; D016196:S Phase / Q000187:drug effects / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology*
D007376:Interleukin-2