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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.

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


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.


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

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