Distinct IL-7 signaling in recent thymic emigrants versus mature naïve T cells controls T-cell homeostasis.
Eur J Immunol
; 46(7): 1669-80, 2016 07.
Article
en En
| MEDLINE
| ID: mdl-27129922
ABSTRACT
IL-7 is essential for T-cell survival but its availability is limited in vivo. Consequently, all peripheral T cells, including recent thymic emigrants (RTEs) are constantly competing for IL-7 to survive. RTEs are required to replenish TCR diversity and rejuvenate the peripheral T-cell pool. However, it remains unknown how RTEs successfully compete with resident mature T cells for IL-7. Moreover, RTEs express low levels of IL-7 receptors, presumably rendering them even less competitive. Here, we show that, surprisingly, RTEs are more responsive to IL-7 than mature naïve T cells as demonstrated by markedly increased STAT5 phosphorylation upon IL-7 stimulation. Nonetheless, adoptive transfer of RTE cells into lymphopenic host mice resulted in slower IL-7-induced homeostatic proliferation and diminished expansion compared to naïve donor T cells. Mechanistically, we found that IL-7 signaling in RTEs preferentially upregulated expression of Bcl-2, which is anti-apoptotic but also anti-proliferative. In contrast, naïve T cells showed diminished Bcl-2 induction but greater proliferative response to IL-7. Collectively, these data indicate that IL-7 responsiveness in RTE is designed to maximize survival at the expense of reduced proliferation, consistent with RTE serving as a subpopulation of T cells rich in diversity but not in frequency.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Timo
/
Transducción de Señal
/
Subgrupos de Linfocitos T
/
Interleucina-7
/
Homeostasis
Límite:
Animals
Idioma:
En
Revista:
Eur J Immunol
Año:
2016
Tipo del documento:
Article
País de afiliación:
Estados Unidos