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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 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 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 Ghosh, P. Articles by Longo, D. L. Search for Related Content PubMed PubMed Citation Articles by Ghosh, P. Articles by Longo, D. L. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 June 2002, Vol. 99, No. 12, pp. 4517-4524 IMMUNOBIOLOGY Effect of rapamycin on the cyclosporin A-resistant CD28-mediated costimulatory pathway Paritosh Ghosh, Meredith A. Buchholz, Shingo Yano, Dennis Taub, and Dan L. Longo From the Lymphocyte Cell Biology Section, Laboratory of Immunology, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD. The consequences of T-cell activation depend exclusively on costimulation during antigen-T-cell receptor interaction. Interaction between the T-cell coreceptor CD28 and its ligand B7 during antigen-antigen receptor engagement results in full activation of T cells, the outcomes of which are proliferation and effector functions. The ability of CD28 to costimulate the production of interleukin-2 (IL-2) explains the importance of this costimulation. The signaling event mediated by CD28 engagement has been proposed to have 2 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 messenger RNA stability and translation, rather than on IL-2 transcription or protein turnover. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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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