Mathematical Models of the Impact of IL2 Modulation Therapies on T Cell Dynamics

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Abstract
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 pleotropic 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.

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