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

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

Author information

1
Department of Surgery and Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA; Program in Immunology, Division of Medical Sciences, Harvard Medical School, Boston, MA 02115, USA.
2
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
3
Department of Surgery and Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.
4
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; The Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
5
Department of Surgery and Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA; Program in Immunology, Division of Medical Sciences, Harvard Medical School, Boston, MA 02115, USA. Electronic address: lturka@partners.org.

Abstract

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

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