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Blood, 1 April 2007, Vol. 109, No. 7, pp. 2894-2902. Prepublished online as a Blood First Edition Paper on December 12, 2006; DOI 10.1182/blood-2006-07-038620. This Article Full Text (PDF) All Versions of this Article: blood-2006-07-038620v1 109/7/2894    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 Deane, J. A. Articles by Fruman, D. A. Search for Related Content PubMed PubMed Citation Articles by Deane, J. A. Articles by Fruman, D. A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 31, 2006 Accepted November 22, 2006 T cell function is partially maintained in the absence of class IA phosphoinositide 3-kinase signaling Jonathan A. Deane, Michael G. Kharas, Jean S. Oak, Linda N. Stiles, Ji Luo, Travis I. Moore, Hong Ji, Christian Rommel, Lewis C. Cantley, Thomas E. Lane, and David A. Fruman* Department of Molecular Biology and Biochemistry, University of California-Irvine, Irvine, CA Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA Serono Pharmaceutical Research Institute, Geneva, Switzerland Department of Systems Biology, Harvard Medical School, Boston, MA Center for Immunology, University of California-Irvine, Irvine, CA * Corresponding author; email: dfruman{at}uci.edu. The class IA subgroup of phosphoinositide 3-kinase (PI3K) is activated downstream of antigen receptors, costimulatory molecules and cytokine receptors on lymphocytes. Targeted deletion of individual genes for class IA regulatory subunits severely impairs the development and function of B cells but not T cells. Here we analyze conditional mutant mice in which thymocytes and T cells lack the major class IA regulatory subunits p85, p55, p50, and p85. These cells exhibit nearly complete loss of PI3K signaling downstream of the T cell receptor (TCR) and CD28. Nevertheless, T cell development is largely unperturbed and peripheral T cells show only partial impairments in proliferation and cytokine production in vitro. Both genetic and pharmacological experiments suggest that class IA PI3K signaling plays a limited role in T cell proliferation driven by TCR/CD28 clustering. In vivo, class IA-deficient T cells provide reduced help to B cells but show normal ability to mediate antiviral immunity. Together these findings provide definitive evidence that class IA PI3K regulatory subunits are essential for a subset of T cell functions, while challenging the notion that this signaling mechanism is a critical mediator of costimulatory signals downstream of CD28. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Fos, A. Salles, V. Lang, F. Carrette, S. Audebert, S. Pastor, M. Ghiotto, D. Olive, G. Bismuth, and J. A. Nunes ICOS Ligation Recruits the p50{alpha} PI3K Regulatory Subunit to the Immunological Synapse J. Immunol., August 1, 2008; 181(3): 1969 - 1977. [Abstract] [Full Text] [PDF] A. J. de Souza, J. S. Oak, R. Jordanhazy, R. H. DeKruyff, D. A. Fruman, and L. P. 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