León Kalet, García-Martínez Karina, Carmenate Tania
Systems Biology Department, Center of Molecular Immunology , Habana , Cuba.
Front Immunol. 2013 Dec 11;4:439. doi: 10.3389/fimmu.2013.00439.
Several reports in the literature have drawn a complex picture of the effect of treatments aiming to modulate IL2 activity in vivo. They seem to promote either immunity or tolerance, probably depending on the specific context, dose, and timing of their application. Such complexity might derive from the pleiotropic role of IL2 in T cell dynamics. To theoretically address the latter possibility, our group has developed several mathematical models for Helper, Regulatory, and Memory T cell population dynamics, which account for most well-known facts concerning their relationship with IL2. We have simulated the effect of several types of therapies, including the injection of: IL2; antibodies anti-IL2; IL2/anti-IL2 immune-complexes; and mutant variants of IL2. We studied the qualitative and quantitative conditions of dose and timing for these treatments which allow them to potentiate either immunity or tolerance. Our results provide reasonable explanations for the existent pre-clinical and clinical data, predict some novel treatments, and further provide interesting practical guidelines to optimize the future application of these types of treatments.
文献中的几篇报告描绘了旨在体内调节IL2活性的治疗效果的复杂图景。它们似乎要么促进免疫，要么促进耐受，这可能取决于其应用的具体背景、剂量和时机。这种复杂性可能源于IL2在T细胞动态中的多效性作用。为了从理论上探讨后一种可能性，我们团队开发了几种关于辅助性T细胞、调节性T细胞和记忆性T细胞群体动态的数学模型，这些模型考虑了与它们和IL2关系相关的大多数已知事实。我们模拟了几种类型治疗的效果，包括注射：IL2；抗IL2抗体；IL2/抗IL2免疫复合物；以及IL2的突变变体。我们研究了这些治疗在剂量和时机方面的定性和定量条件，这些条件使它们能够增强免疫或耐受。我们的结果为现有的临床前和临床数据提供了合理的解释，预测了一些新的治疗方法，并进一步为优化这些类型治疗的未来应用提供了有趣的实用指南。
