Submitted June 13, 2006
Accepted September 19, 2006
IL-7-induced proliferation of recent thymic emigrants requires activation of the PI3K pathway
Louise Swainson, Sandrina Kinet, Cedric Mongellaz, Marion Sourisseau, Telmo Henriques, and Naomi Taylor*
Institut de Genetique Moleculaire de Montpellier, Montpellier, France
* Corresponding author; email: taylor{at}igmm.cnrs.fr.
The IL-7 cytokine promotes the survival of a diverse T cell pool, thereby ensuring an efficient immune response. Moreover, IL-7 induces the proliferation of recent thymic emigrants (RTE) in neonates. Here, we demonstrate that the survival and proliferative effects of IL-7 on human RTE can be distinguished, on the basis of dose as well as duration of IL-7 administration. A dose of 0.1 ng/ml of IL-7 is sufficient to promote viability whereas cell cycle entry is observed only at doses higher than 1 ng/ml. Moreover, a short 1h exposure to high dose IL-7 (10 ng/ml) induces long-term survival but continuous IL-7 exposure is necessary for optimal cell cycle entry and proliferation. We find that distinct signaling intermediates are activated under conditions of IL-7-induced survival and proliferation: STAT5 tyrosine phosphorylation does not correlate with proliferation whereas upregulation of the glucose transporter Glut-1 as well as increased glucose uptake are markers of IL-7-induced cell cycle entry. Glut-1 is directly regulated by PI3K and indeed, inhibiting PI3K activity abrogates IL-7-induced proliferation. Our finding that the survival and proliferation of RTE are differentially modulated by the dose and kinetics of exogenous IL-7 has important implications for the clinical use of this cytokine.
