Figure 1.

Scheme of the T Cell Response Model and Adaptive Dosing IL-2 Therapy

IL-2 concentration and the population of two T-cell subsets, Tconvs and Tregs, are the immune variables considered in the mathematical model (1). Naïve Tconvs and resting Tregs originated from thymic selection are under homeostatic turnover in the periphery. Upon Ag stimulation provided by APCs, naïve Tconvs and resting Tregs become activated. In contrast to activated Tconvs, activated Tregs do not secrete IL-2, but both activated populations proliferate in dependence on the presence of IL-2. Activated Tregs suppress activated Tconvs in a cell contact–dependent and cytokine-driven manner. In contrast to Tregs, activated Tconvs undergo Fas-induced apoptosis by interacting with each other (fratricide). All cells undergo natural cell death and IL-2 is degraded. In the context of IL-2 therapy, the control unit provides the next optimal IL-2 dose according to a feedback from the current status of the immune variables. The control unit calculates the IL-2 dose that is needed to keep T-cell numbers and systemic IL-2 concentration in a predefined range (clinical constraints). Adoptive Treg transfer is the therapeutic process of increasing Treg numbers in the immune system by transiently transferring Tregs to the individual.