Agent-Based Model of Heterogeneous T-Cell Activation in Vitro

We combine modelling and in vitro measurement of T-cell properties at the level of individual cells. Rather than seek to model kinetics using one differential equation per cell population, our computational model describes the dynamics of a cohort of cells in terms of a series of discrete events, one after the other, occurring to one cell at a time. Two types of heterogeneity are explicitly simulated: cell surface marker expression that is time-dependent and varies from cell to cell and spatial heterogeneity that arises from local influences such as the proximity of IL-2-producing cells. Neither storing 50,000 individual cell instances and their attributes nor following the kinetics over times of order 48 h and producing simulated flow cytometry plots, is too taxing for a modern desktop computer. In vitro, the kinetics of the activation of cohorts of CD4+ T cells from BALB/c mice was studied, under stimulus with soluble or plate-bound anti-CD3 or a combination of PMA and ionomycin.