An analysis of early-stage IL-2 capture times in populations of T cells diffusively interacting in a confined environment

• A methodology is presented for calculating the effects of diffusive interactions in large populations of Th and Treg cells. The premise of this work is the behavior of a confined representative subpopulation reflects that of the entire population.
• This methodology is used to examine the effects of early-stage competition among the cells for IL-2 secreted by the Th.
• Typical Tregs are good IL-2 scavengers but their effect on autocrine capture is shorter-ranged than previously reported.
• Correlations are provided for estimating IL-2 autocrine and paracrine capture over a wide range of conditions.

This numerical analysis examines early-stage Interlukin-2 (IL-2) capture in large populations of secreting T helper (Th) and absorbing T regulatory (Treg) cells in an attempt to provide rational guidelines for when diffusive interactions can affect the Th autocrine cycle, as reflected in capture times. Autocrine and paracrine capture is calculated over a wide range of conditions: the mix of cells in a population; cell size and spacing; antigen activated IL-2 secretion and Th receptor expression rates; receptor dissociation constant; and number of resting Treg receptors. Correlations for quickly estimating IL-2 capture over these conditions are provided. This study suggests that a typical Treg can scavenge a significant amount of IL-2 without affecting autocrine capture by the Th. As a result, Treg influence on autocrine capture is shorter-ranged than previously reported. It is conjectured that high early-stage paracrine relative to autocrine capture leads to faster receptor enhancement for a Treg than a Th. The resulting enhancement time gap is considerably longer and, thus, diffusive suppression more likely, for a weakly- as opposed to strongly-activated Th. The methodology can be extended to later-stage capture to confirm this conjecture and to diffusive interactions in other cell-type populations.