Human naïve regulatory T-cells feature high steady-state turnover and are maintained by IL-7

Oncotarget. 2016 Mar 15;7(11):12163-75. doi: 10.18632/oncotarget.7512.


Naïve FoxP3-expressing regulatory T-cells (Tregs) are essential to control immune responses via continuous replenishment of the activated-Treg pool with thymus-committed suppressor cells. The mechanisms underlying naïve-Treg maintenance throughout life in face of the age-associated thymic involution remain unclear. We found that in adults thymectomized early in infancy the naïve-Treg pool is remarkably well preserved, in contrast to conventional naïve CD4 T-cells. Naïve-Tregs featured high levels of cycling and pro-survival markers, even in healthy individuals, and contrasted with other circulating naïve/memory CD4 T-cell subsets in terms of their strong γc-cytokine-dependent signaling, particularly in response to IL-7. Accordingly, ex-vivo stimulation of naïve-Tregs with IL-7 induced robust cytokine-dependent signaling, Bcl-2 expression, and phosphatidylinositol 3-kinase (PI3K)-dependent proliferation, whilst preserving naïve phenotype and suppressive capacity. Altogether, our data strongly implicate IL-7 in the thymus-independent long-term survival of functional naïve-Tregs, and highlight the potential of targeting the IL-7 pathway to modulate Tregs in different clinical settings.

Keywords: IL-7; Immune response; Immunity; Immunology and Microbiology Section; human regulatory T-cells; naïve regulatory T-cells; regulatory T-cell homeostasis; thymectomy.

MeSH terms

  • Adolescent
  • Adult
  • Cell Survival / immunology
  • Forkhead Transcription Factors / immunology
  • Humans
  • Interleukin-7 / immunology*
  • T-Lymphocytes, Regulatory / cytology*
  • T-Lymphocytes, Regulatory / immunology*
  • Young Adult


  • Forkhead Transcription Factors
  • IL7 protein, human
  • Interleukin-7