IL-7–induced proliferation of recent thymic emigrants requires activation of the PI3K pathway - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement
Article Dans Une Revue Blood Année : 2006

IL-7–induced proliferation of recent thymic emigrants requires activation of the PI3K pathway

Résumé

Abstract 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 (RTEs) in neonates. Here, we demonstrate that the survival and proliferative effects of IL-7 on human RTEs can be distinguished on the basis of dose as well as duration of IL-7 administration. A dose of 0.1 ng/mL IL-7 is sufficient to promote viability, whereas cell-cycle entry is observed only at doses higher than 1 ng/mL. Moreover, a short 1-hour 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 up-regulation 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 RTEs are differentially modulated by the dose and kinetics of exogenous IL-7 has important implications for the clinical use of this cytokine.

Domaines

Immunologie

Dates et versions

hal-04181115 , version 1 (14-08-2023)

Identifiants

Citer

Louise Swainson, Sandrina Kinet, Cedric Mongellaz, Marion Sourisseau, Telmo Henriques, et al.. IL-7–induced proliferation of recent thymic emigrants requires activation of the PI3K pathway. Blood, 2006, 109 (3), pp.1034-1042. ⟨10.1182/blood-2006-06-027912⟩. ⟨hal-04181115⟩
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