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Blood, 1 February 2007, Vol. 109, No. 3, pp. 1034-1042. Prepublished online as a Blood First Edition Paper on October 5, 2006; DOI 10.1182/blood-2006-06-027912. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2006-06-027912v1 109/3/1034    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Swainson, L. Articles by Taylor, N. Search for Related Content PubMed PubMed Citation Articles by Swainson, L. Articles by Taylor, N. Social Bookmarking                   What's this?  Previous Article  |  Next Article  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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Beq, S. Rozlan, D. Gautier, R. Parker, V. Mersseman, C. Schilte, B. Assouline, I. Rance, P. Lavedan, M. Morre, et al. Injection of glycosylated recombinant simian IL-7 provokes rapid and massive T-cell homing in rhesus macaques Blood, July 23, 2009; 114(4): 816 - 825. [Abstract] [Full Text] [PDF] S. J. Opiela, T. Koru-Sengul, and B. Adkins Murine neonatal recent thymic emigrants are phenotypically and functionally distinct from adult recent thymic emigrants Blood, May 28, 2009; 113(22): 5635 - 5643. [Abstract] [Full Text] [PDF] R. I. Azevedo, M. V. D. Soares, J. T. Barata, R. Tendeiro, A. Serra-Caetano, R. M. M. Victorino, and A. E. Sousa IL-7 sustains CD31 expression in human naive CD4+ T cells and preferentially expands the CD31+ subset in a PI3K-dependent manner Blood, March 26, 2009; 113(13): 2999 - 3007. [Abstract] [Full Text] [PDF] A. M. Crawley, T. Katz, K. Parato, and J. B. Angel IL-2 receptor {gamma} chain cytokines differentially regulate human CD8+CD127+ and CD8+CD127- T cell division and susceptibility to apoptosis Int. Immunol., January 1, 2009; 21(1): 29 - 42. [Abstract] [Full Text] [PDF] N. J. MacIver, S. R. Jacobs, H. L. Wieman, J. A. Wofford, J. L. Coloff, and J. C. Rathmell Glucose metabolism in lymphocytes is a regulated process with significant effects on immune cell function and survival J. Leukoc. Biol., October 1, 2008; 84(4): 949 - 957. [Abstract] [Full Text] [PDF] S. E. Johnson, N. Shah, A. A. Bajer, and T. W. LeBien IL-7 Activates the Phosphatidylinositol 3-Kinase/AKT Pathway in Normal Human Thymocytes but Not Normal Human B Cell Precursors J. Immunol., June 15, 2008; 180(12): 8109 - 8117. [Abstract] [Full Text] [PDF] J. Garaude, R. Farras, G. Bossis, S. Charni, M. Piechaczyk, R. A. Hipskind, and M. Villalba SUMOylation Regulates the Transcriptional Activity of JunB in T Lymphocytes J. Immunol., May 1, 2008; 180(9): 5983 - 5990. [Abstract] [Full Text] [PDF] J. A. Wofford, H. L. Wieman, S. R. Jacobs, Y. Zhao, and J. C. Rathmell IL-7 promotes Glut1 trafficking and glucose uptake via STAT5-mediated activation of Akt to support T-cell survival Blood, February 15, 2008; 111(4): 2101 - 2111. [Abstract] [Full Text] [PDF]

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