Khailaie Sahamoddin, Montaseri Ghazal, Meyer-Hermann Michael
Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Centre for Individualised Infection Medicine (CIIM), Hannover, Germany.
iScience. 2020 Oct 12;23(11):101663. doi: 10.1016/j.isci.2020.101663. eCollection 2020 Nov 20.
Regulatory 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. results suggested that a combination of IL-2 and adoptive Treg transfer therapies can limit this side effect.
调节性T细胞（Treg）是一种抑制性细胞，可控制自身反应性和过度效应性常规辅助性T细胞（Tconv）反应。Treg和Tconv之间平衡的破坏是自身免疫性疾病和炎症性疾病的一个标志。白细胞介素-2（IL-2）是这两种细胞群体的生长因子，在IL-2治疗中可通过微调来恢复健康的免疫平衡。通过使用一个机理数学模型，我们引入了一种自适应控制策略，以设计增加和稳定Treg群体并限制炎症反应所需的最小治疗性IL-2剂量。这种自适应方案允许根据患者免疫动力学的反馈进行剂量调整。我们的模拟结果表明，需要最小的Treg群体来限制IL-2注射对效应性Tconv反应的短暂副作用。结果表明，IL-2和过继性Treg转移疗法的联合应用可以限制这种副作用。
