Differential Roles of IL-2 Signaling in Developing versus Mature Tregs

Cell Rep. 2018 Oct 30;25(5):1204-1213.e4. doi: 10.1016/j.celrep.2018.10.002.


Although Foxp3+ regulatory T cells (Tregs) require interleukin-2 (IL-2) for their development, it has been unclear whether continuing IL-2 signals are needed to maintain lineage stability, survival, and suppressor function in mature Tregs. We generated mice in which CD25, the main ligand-binding subunit of the IL-2 receptor, can be inducibly deleted from Tregs after thymic development. In contrast to Treg development, we find that IL-2 is dispensable for maintaining lineage stability in mature Tregs. Although continuous IL-2 signaling is needed for long-term Treg survival, CD25-deleted Tregs may persist for several weeks in vivo using IL-7. We also observe defects in glycolytic metabolism and suppressor function following CD25 deletion. Thus, unlike developing Tregs in which the primary role of IL-2 is to initiate Foxp3 expression, mature Tregs require continuous IL-2 signaling to maintain survival and suppressor function, but not to maintain lineage stability.

Keywords: CD25; IL-15; IL-2; IL-7; regulatory T cell.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation*
  • Cell Lineage
  • Cell Survival
  • Forkhead Transcription Factors / metabolism
  • Gene Deletion
  • Glycolysis
  • Interleukin-2 / metabolism*
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Interleukin-7 / metabolism
  • Mice, Knockout
  • Phenotype
  • Signal Transduction*
  • T-Lymphocytes, Regulatory / cytology*
  • T-Lymphocytes, Regulatory / metabolism*


  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Interleukin-2
  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-7