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Prepublished online as a Blood First Edition Paper on April 17, 2002; DOI 10.1182/blood-2001-11-0062. This Article Full Text (PDF) All Versions of this Article: 2001-11-0062v1 99/12/4517    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 Ghosh, P. Articles by Longo, D. L Search for Related Content PubMed PubMed Citation Articles by Ghosh, P. Articles by Longo, D. L Social Bookmarking                   What's this? Submitted November 27, 2001 Accepted February 11, 2002 Effect of rapamycin on the cyclosporin A-resistant CD28-mediated co-stimulatory pathway Paritosh Ghosh*, Meredith A Buchholz, Shingo Yano, Dennis Taub, and Dan L Longo Laboratory of Immunology, National Institute on Aging, Baltimore, MD, USA * Corresponding author; email: ghoshp{at}grc.nia.nih.gov. The consequences of T cell activation depend exclusively on co-stimulation during antigen-T cell receptor interaction. Interaction between the T cell co-receptor CD28 and its ligand B7 during antigen-antigen receptor engagement results in full activation of T cells, the outcomes of which are proliferation and generation of effector functions. The ability of CD28 to co-stimulate the production of interleukin-2 (IL-2) explains the importance of this co-stimulation. The signaling event mediated by CD28 engagement has been proposed to have two components: one is sensitive to the immunosuppressive drug cyclosporin A (CsA), and the other one is CsA-resistant. In this report, we demonstrate that the CsA-resistant pathway is sensitive to the immunosuppressive drug rapamycin. Treatment with rapamycin blocked IL-2 production after activation of human peripheral blood T cells with phorbol ester (PMA) and anti-CD28 (CsA-resistant pathway), whereas this drug did not have any effect on PMA plus ionomycin stimulation (CsA-sensitive pathway). The inhibitory effect of rapamycin was on mRNA stability and translation, rather than on IL-2 transcription or protein turnover. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. Scheinberg, C. O. Wu, O. Nunez, P. Scheinberg, C. Boss, E. M. Sloand, and N. S. Young Treatment of severe aplastic anemia with a combination of horse antithymocyte globulin and cyclosporine, with or without sirolimus: a prospective randomized study Haematologica, March 1, 2009; 94(3): 348 - 354. [Abstract] [Full Text] [PDF] N. J. Bahlis, A. M. King, D. Kolonias, L. M. Carlson, H. Y. Liu, M. A. Hussein, H. R. Terebelo, G. E. Byrne Jr, B. L. Levine, L. H. Boise, et al. CD28-mediated regulation of multiple myeloma cell proliferation and survival Blood, June 1, 2007; 109(11): 5002 - 5010. [Abstract] [Full Text] [PDF] M. Zeyda, R. Geyeregger, M. Poglitsch, T. Weichhart, G. J. Zlabinger, S. Koyasu, W. H. Horl, T. M. Stulnig, B. Watschinger, and M. D. Saemann Impairment of T cell interactions with antigen-presenting cells by immunosuppressive drugs reveals involvement of calcineurin and NF-{kappa}B in immunological synapse formation J. Leukoc. Biol., January 1, 2007; 81(1): 319 - 327. [Abstract] [Full Text] [PDF] C. Y. Sasaki, T. J. Barberi, P. Ghosh, and D. L. Longo Phosphorylation of RelA/p65 on Serine 536 Defines an I{kappa}B{alpha}-independent NF-{kappa}B Pathway J. Biol. Chem., October 14, 2005; 280(41): 34538 - 34547. [Abstract] [Full Text] [PDF] M. H. Albert, X.-Z. Yu, P. J. Martin, and C. Anasetti Prevention of lethal acute GVHD with an agonistic CD28 antibody and rapamycin Blood, February 1, 2005; 105(3): 1355 - 1361. [Abstract] [Full Text] [PDF] H. Kusaba, P. Ghosh, R. Derin, M. Buchholz, C. Sasaki, K. Madara, and D. L. Longo Interleukin-12-induced Interferon-{gamma} Production by Human Peripheral Blood T Cells Is Regulated by Mammalian Target of Rapamycin (mTOR) J. Biol. Chem., January 14, 2005; 280(2): 1037 - 1043. [Abstract] [Full Text] [PDF] L. X. Wu, J. La Rose, L. Chen, C. Neale, T. Mak, K. Okkenhaug, R. Wange, and R. Rottapel CD28 Regulates the Translation of Bcl-xL via the Phosphatidylinositol 3-Kinase/Mammalian Target of Rapamycin Pathway J. Immunol., January 1, 2005; 174(1): 180 - 194. [Abstract] [Full Text] [PDF] G. Yu, H. Luo, Y. Wu, and J. Wu EphrinB1 Is Essential in T-cell-T-cell Co-operation during T-cell Activation J. Biol. Chem., December 31, 2004; 279(53): 55531 - 55539. [Abstract] [Full Text] [PDF] G. Yu, H. Luo, Y. Wu, and J. Wu Mouse EphrinB3 Augments T-cell Signaling and Responses to T-cell Receptor Ligation J. Biol. Chem., November 21, 2003; 278(47): 47209 - 47216. [Abstract] [Full Text] [PDF]

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