Fig. 4.

A circuit that produces a robust amount of differentiated cells by endocytosis of a cytokine by the precursor cells. (A) Schematic of a circuit in which cytokine c enhances the differentiation of X₁ cells from precursor cells X₀. The precursors also remove c by endocytosis. (B) An example of the circuit in differentiation of T-helper cells: CD4⁺ cells differentiation to T-helper cells (e.g., Th2 cells) is enhanced by IL-2. However, Treg cell level is roughly proportional to the CD4⁺ pool (5–10% of CD4⁺ levels; proportionality is marked as a dotted arrow). Tregs take up IL-2, thus reducing its levels. (C) Dynamics of X₁ cell concentration reach a homeostatic steady state that is independent of the levels of precursors X₀. Different lines represent different X₀ levels (contrast with Fig. 1C). Here, α = β₀ = 1, β₃ = 3, α₁ = 2, f(c) = c /c + 3, X₁(0) = 1, and c(0) = 10.