Author(s): Silva, Susana L. ; Albuquerque, Adriana S. ; Serra-Caetano, Ana ; Foxall, Russell B. ; Pires, Ana R. ; Matoso, Paula ; Fernandes, Susana M. ; Ferreira, João ; Cheynier, Rémi ; Victorino, Rui M. M. ; Caramalho, Iris ; Barata, João T. ; Sousa, Ana E.
Date: 2016
Persistent ID: http://hdl.handle.net/10451/24384
Origin: Repositório da Universidade de Lisboa
Subject(s): IL-7; Immune response; Human regulatory T-cells; Naïve regulatory T-cells; Regulatory T-cell homeostasis; Thymectomy
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.
