In this review we discuss how the competition for cytokines between different cells of the immune system can shape the system wide immune response. We focus on interleukin-2 (IL-2) secretion by activated effector T cells (T(eff)) and on the competition for IL-2 consumption between T(eff) and regulatory T cells (T(reg)). We discuss the evidence for the mechanism in which the depletion of IL-2 by T(reg) cells would be sufficient to suppress an autoimmune response, yet not strong enough to prevent an immune response. We present quantitative estimations and summarize our modeling effort to show that the tug-of-war between T(reg) and T(eff) cells for IL-2 molecules can be won by T(reg) cells in the case of weak activation of T(eff) leading to the suppression of the immune response. Or, for strongly activated T(eff) cells, it can be won by T(eff) cells bringing about the activation of the whole adaptive immune system. Finally, we discuss some recent applications attempting to achieve clinical effects through the modulation of IL-2 consumption by T(reg) compartment.
Keywords: IL-2; computational modeling; cytokine competition; regulatory T cells; systems immunology.