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Blood, 15 March 2006, Vol. 107, No. 6, pp. 2415-2422. Prepublished online as a Blood First Edition Paper on November 22, 2005; DOI 10.1182/blood-2005-08-3300. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 2005-08-3300v1 107/6/2415    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Swat, W. Articles by Diacovo, T. G. Search for Related Content PubMed PubMed Citation Articles by Swat, W. Articles by Diacovo, T. G. Related Collections Immunobiology Apoptosis Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Essential role of PI3K and PI3K in thymocyte survival Wojciech Swat, Vivianne Montgrain, Teresa A. Doggett, Jason Douangpanya, Kamal Puri, William Vermi, and Thomas G. Diacovo From the Department of Pathology and Immunology and the Department of Pediatrics, Washington University School of Medicine, St Louis, MO; ICOS Corp, Bothell, WA; the Department of Pathology, University of Bresica, Italy; and the Departments of Pediatrics and Pathology, Columbia University, New York, NY. Class 1 phosphoinositide 3-kinases (PI3Ks), consisting of PI3K, , , and , are a family of intracellular signaling molecules that play important roles in cell-mediated immune responses. In thymocytes, however, their role is less clear, although PI3K is postulated to partially contribute to pre-TCR-dependent differentiation. We now report that PI3K, in conjunction with PI3K, is required for thymocyte survival and ultimately for T-cell production. Surprisingly, genetic deletion of the p110 and p110 catalytic subunits resulted in a dramatic reduction in thymus size, cellularity, and lack of corticomedullary differentiation. Total thymocyte counts in these animals were 27-fold lower than in wild-type (WT) controls because of a diminished number of CD4+CD8+ double-positive (DP) cells and were associated with T-cell depletion in blood and in secondary lymphoid organs. Moreover, this alteration in the DP population was intrinsic to thymocytes, because the reconstitution of p110-/- animals with WT fetal liver cells restored the proportions of all thymocyte populations to those in WT controls. The observed defects were related to massive apoptosis in the DP population; TCRB expression, pre-TCR selection, and generation of DP cells appeared relatively unperturbed. Thus, class 1 PI3Ks work in concert to protect developing thymocytes from apoptosis. (Blood. 2006;107:2415-2422) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Srivastava, L. Di, O. Zhdanova, Z. Li, S. Vardhana, Q. Wan, Y. Yan, R. Varma, J. Backer, H. Wulff, et al. The Class II Phosphatidylinositol 3 kinase C2{beta} Is Required for the Activation of the K+ Channel KCa3.1 and CD4 T-Cells Mol. Biol. Cell, September 1, 2009; 20(17): 3783 - 3791. [Abstract] [Full Text] [PDF] A. Saudemont, F. Garcon, H. Yadi, M. Roche-Molina, N. Kim, A. Segonds-Pichon, A. Martin-Fontecha, K. Okkenhaug, and F. Colucci p110{gamma} and p110{delta} isoforms of phosphoinositide 3-kinase differentially regulate natural killer cell migration in health and disease PNAS, April 7, 2009; 106(14): 5795 - 5800. [Abstract] [Full Text] [PDF] M. Rajasagi, M. Vitacolonna, B. Benjak, R. Marhaba, and M. Zoller CD44 promotes progenitor homing into the thymus and T cell maturation J. Leukoc. Biol., February 1, 2009; 85(2): 251 - 261. [Abstract] [Full Text] [PDF] F. Garcon, D. T. Patton, J. L. Emery, E. Hirsch, R. Rottapel, T. Sasaki, and K. Okkenhaug CD28 provides T-cell costimulation and enhances PI3K activity at the immune synapse independently of its capacity to interact with the p85/p110 heterodimer Blood, February 1, 2008; 111(3): 1464 - 1471. [Abstract] [Full Text] [PDF] I. Alcazar, M. Marques, A. Kumar, E. Hirsch, M. Wymann, A. C. Carrera, and D. F. Barber Phosphoinositide 3 kinase {gamma} participates in T cell receptor induced T cell activation J. Exp. Med., November 26, 2007; 204(12): 2977 - 2987. [Abstract] [Full Text] [PDF] N. Kim, A. Saudemont, L. Webb, M. Camps, T. Ruckle, E. Hirsch, M. Turner, and F. Colucci The p110delta catalytic isoform of PI3K is a key player in NK-cell development and cytokine secretion Blood, November 1, 2007; 110(9): 3202 - 3208. [Abstract] [Full Text] [PDF] H. Ji, F. Rintelen, C. Waltzinger, D. Bertschy Meier, A. Bilancio, W. Pearce, E. Hirsch, M. P. Wymann, T. Ruckle, M. Camps, et al. Inactivation of PI3K{gamma} and PI3K{delta} distorts T-cell development and causes multiple organ inflammation Blood, October 15, 2007; 110(8): 2940 - 2947. [Abstract] [Full Text] [PDF] M. M. Juntilla, J. A. Wofford, M. J. Birnbaum, J. C. Rathmell, and G. A. Koretzky Akt1 and Akt2 are required for {alpha}beta thymocyte survival and differentiation PNAS, July 17, 2007; 104(29): 12105 - 12110. [Abstract] [Full Text] [PDF] C. Mao, E. G. Tili, M. Dose, M. C. Haks, S. E. Bear, I. Maroulakou, K. Horie, G. A. Gaitanaris, V. Fidanza, T. Ludwig, et al. Unequal Contribution of Akt Isoforms in the Double-Negative to Double-Positive Thymocyte Transition J. Immunol., May 1, 2007; 178(9): 5443 - 5453. [Abstract] [Full Text] [PDF] J. A. Deane, M. G. Kharas, J. S. Oak, L. N. Stiles, J. Luo, T. I. Moore, H. Ji, C. Rommel, L. C. Cantley, T. E. Lane, et al. T-cell function is partially maintained in the absence of class IA phosphoinositide 3-kinase signaling Blood, April 1, 2007; 109(7): 2894 - 2902. [Abstract] [Full Text] [PDF] F. Shiroki, S. Matsuda, T. Doi, M. Fujiwara, Y. Mochizuki, T. Kadowaki, H. Suzuki, and S. Koyasu The p85{alpha} Regulatory Subunit of Class IA Phosphoinositide 3-Kinase Regulates beta-Selection in Thymocyte Development J. Immunol., February 1, 2007; 178(3): 1349 - 1356. [Abstract] [Full Text] [PDF]

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