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

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

Author information

1
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
2
Clínica Universitária de Imunoalergologia, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisboa, Portugal.
3
Clínica Universitária de Medicina II, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisboa, Portugal.
4
Infection, Immunity and Inflammation Department, Institut Cochin, INSERM U1016-CNRS UMR8104-Université Paris Descartes, Paris, France.

Abstract

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

PMID:
26910841
PMCID:
PMC4914276
DOI:
10.18632/oncotarget.7512
[Indexed for MEDLINE]
Free PMC Article

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