摘要：SummaryRegulatory T cells (Treg) are suppressor cells that control self-reactive and excessive effector conventional T helper cell (Tconv) responses. Breakdown of the balance between Tregs and Tconvs is a hallmark of autoimmune and inflammatory diseases. Interleukin-2 (IL-2) is a growth factor for both populations and subtle leverage to restore the healthy immune balance in IL-2 therapy. By using a mechanistic mathematical model, we introduced an adaptive control strategy to design the minimal therapeutic IL-2 dosage required to increase and stabilize Treg population and restrict inflammatory response. This adaptive protocol allows for dose adjustments based on the feedback of the immune kinetics of the patient. Our simulation results showed that a minimal Treg population was required to restrict the transient side effect of IL-2 injections on the effector Tconv response.In silicoresults suggested that a combination of IL-2 and adoptive Treg transfer therapies can limit this side effect.Graphical AbstractDisplay OmittedHighlights•An adaptive dosing strategy for IL-2 therapy is introduced and analyzedin silico•IL-2 injections can be tuned to increase and stabilize regulatory T-cell numbers•Immunosuppressive IL-2 therapy may transiently exacerbate effector T-cell responses•Combined IL-2 and adoptive regulatory T-cell therapy can safely limit inflammationBiological Sciences; Immunology; Mathematical Bioscience
