Foxp3+ Regulatory T-cells and IL-2: The Moirai of T-cell Fates?

Regulatory T-cells (T reg ) have emerged as a crucial cellular checkpoint acting to prevent potentially harmful immune responses. Due to its highly diverse activities, regulating the immune system requires more than general suppression. Particularly, during the developing immune response to infection, T reg need to balance the host reaction to achieve both an effective response against the invading pathogen as well as to prevent immunopathology from excessive or inappropriate activity. In this opinion article we discuss the dual roles of IL-2 as both a key inducer of T reg activity and also a target of T reg control during the acute phase of infection. We propose a model in which Foxp3+ regulatory T-cells dynamically "measure" IL-2 availability and restrict its access to effector T-cells, thereby controlling differentiation of these useful but potentially harmful cells.