Figure 6
Model for the tuning of IL-2 signaling by ADP-ribosylation of CD25.
(a) Tregs constitutively express high levels of CD25 while CD8+ T cells and NK cells express only the β and γ chains of the IL-2 receptor (CD132, CD122). In a non-inflammatory environment, Tregs consume IL-2 due to the higher affinity of CD25 compared to CD122/CD132, thereby depriving neighboring CD8 cells and NK cells of this cytokine. (b) In an inflammatory environment, i.e. following the release of NAD+ from damaged cells, ADP-ribosylation of CD25 (blue circles) diverts IL-2 from the high affinity receptor to the low affinity β and γ chains, allowing efficient expansion of CD8 cells and NK cells. (c) Systemic injection of IL-2 in complex with antibodies that prevent binding of IL-2 to CD25 similarly results in preferential expansion of CD8 cells and NK cells.
