Fig 2. The model captures the distribution of Th effector types in vitro in the presence and absence of cytokine signaling, due to an underlying bifurcation in the dynamical system.

All data are from [34]. Experiments and the model were both run at 2*10⁶ cells/mL. (a) When cytokines accumulate unhindered, a uniform distribution of Th1, Th2, and mixed effector types is observed, as measured by the balance of T-bet and GATA3 expression, across 1000 sample paths of the SDE system. This closely matches empirical observations (inset). (b) When cytokine accumulation is blocked, a U-shaped distribution of Th1 and Th2 effector types is observed across 1000 sample paths of the SDE system. This also closely matches empirical observations (inset). (c) Analysis of the ODE system shows that mixed effector types are only stable in the presence of cytokine signaling. As cytokine secretion is removed from the model, the mixed effector type becomes unstable and bifurcates into polarized Th1 and Th2 effector types.