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Blood, 1 February 2008, Vol. 111, No. 3, pp. 1464-1471. Prepublished online as a Blood First Edition Paper on November 15, 2007; DOI 10.1182/blood-2007-08-108050. This Article Full Text Full Text (PDF) Supplemental Figures and Videos All Versions of this Article: blood-2007-08-108050v1 111/3/1464    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 Garçon, F. Articles by Okkenhaug, K. Search for Related Content PubMed PubMed Citation Articles by Garçon, F. Articles by Okkenhaug, K. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY CD28 provides T-cell costimulation and enhances PI3K activity at the immune synapse independently of its capacity to interact with the p85/p110 heterodimer Fabien Garçon1, Daniel T. Patton1, Juliet L. Emery1, Emilio Hirsch2, Robert Rottapel3, Takehiko Sasaki4, and Klaus Okkenhaug1 1 Laboratory of Lymphocyte Signaling and Development, Babraham Institute, Babraham Research Campus, Cambridge, United Kingdom; 2 Department of Genetics, Biology and Biochemistry, University of Turin, Turin, Italy; 3 Princess Margaret Hospital/Ontario Cancer Institute, Toronto, ON; 4 Department of Pathology and Immunology, Akita University School of Medicine, Akita, Japan Activation of PI3K is among the earliest signaling events observed in T cells after conjugate formation with antigen-presenting cells (APCs). The relevant PI3K catalytic isoform and relative contribution of the TcR and CD28 to PI3K activity at the immune synapse have not been determined unequivocally. Using a quantitative imaging-based assay, we show that the PI3K activity at the T cell–APC contact area is dependent on the p110, but not the p110, isoform of PI3K. CD28 enhanced PIP3 production at the T-cell synapse independently of its YMNM PI3K-recruitment motif that instead was required for efficient PKC recruitment. CD28 could partially compensate for the lack of p110 activity during T-cell activation, which indicates that CD28 and p110 act in parallel and complementary pathways to activate T cells. Consistent with this, CD28 and p110 double-deficient mice were severely immune compromised. We therefore suggest that combined pharmaceutic targeting of p110 activity and CD28 costimulation has potent therapeutic potential. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Waugh, L. Sinclair, D. Finlay, J. R. Bayascas, and D. Cantrell Phosphoinositide (3,4,5)-Triphosphate Binding to Phosphoinositide-Dependent Kinase 1 Regulates a Protein Kinase B/Akt Signaling Threshold That Dictates T-Cell Migration, Not Proliferation Mol. Cell. Biol., November 1, 2009; 29(21): 5952 - 5962. [Abstract] [Full Text] [PDF] C.-H. Hsieh, J.-T. Hsu, Y.-C. Hsieh, M. Frink, R. Raju, W. J. Hubbard, K. I. Bland, and I. H. Chaudry Suppression of Activation and Costimulatory Signaling in Splenic CD4+ T Cells after Trauma-Hemorrhage Reduces T-Cell Function: A Mechanism of Post-Traumatic Immune Suppression Am. J. Pathol., October 1, 2009; 175(4): 1504 - 1514. [Abstract] [Full Text] [PDF] K. Gollmer, F. Asperti-Boursin, Y. Tanaka, K. Okkenhaug, B. Vanhaesebroeck, J. R. Peterson, Y. Fukui, E. Donnadieu, and J. V. Stein CCL21 mediates CD4+ T-cell costimulation via a DOCK2/Rac-dependent pathway Blood, July 16, 2009; 114(3): 580 - 588. 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