SEARCH:   Advanced

Blood, 15 October 2004, Vol. 104, No. 8, pp. 2418-2424. Prepublished online as a Blood First Edition Paper on June 17, 2004; DOI 10.1182/blood-2004-04-1294. This Article Full Text (PDF) All Versions of this Article: 2004-04-1294v1 104/8/2418    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 Mirandola, P. Articles by Vitale, M. Search for Related Content PubMed PubMed Citation Articles by Mirandola, P. Articles by Vitale, M. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 6, 2004 Accepted May 26, 2004 Activated human NK and CD8+ T cells express both TNF-related apoptosis inducing ligand (TRAIL) and TRAIL receptors, but are resistant to TRAIL-mediated cytotoxicity Prisco Mirandola, Cristina Ponti, Giuliana Gobbi, Ivonne Sponzilli, Mauro Vaccarezza, Lucio Cocco, Giorgio Zauli, Paola Secchiero, Francesco A Manzoli, and Marco Vitale* Department of Anatomy, Pharmacology & Forensic Medicine, Human Anatomy Section, University of Parma, Parma, Italy Department of Anatomical Sciences, Cellular Signalling Laboratory, University of Bologna, Bologna, Italy Department of Normal Human Morphology, University of Trieste, Trieste, Italy Department of Morphology and Embriology, Human Anatomy Section, University of Ferrara, Ferrara, Italy Department of Anatomy, Pharmacology & Forensic Medicine, Human Anatomy Section, University of Parma, Parma, Italy; Research Institute Codivilla-Putti, IOR, ITOI-CNR, Bologna Unit, Bologna, Italy * Corresponding author; email: marco.vitale{at}unipr.it. The expression of TRAIL and TRAIL receptors was investigated in resting and cytokine-activated purified primary human NK and CD8+T cells. Resting NK and CD8+T cells expressed the mRNA for all TRAIL receptors, but TRAIL-R4 was the only receptor clearly detectable on the surface of both cell types. NK cells were activated by IL-2 or IL-15, while CD8+T cells by PHA+IL-2 followed by IL-2 alone for up to 10 days. Upon activation, both cell types rapidly expressed TRAIL-R2 and TRAIL-R3, whose expression peaked at day 10 of culture. TRAIL-R1, however, was never expressed at any time point examined, while the expression of TRAIL-R4, that showed a progressive increase in CD8+T cells, remained constant in NK cells. Notwithstanding the expression of TRAIL-R2, recombinant TRAIL did not show any cytotoxic activity on either NK or CD8+T cells. Both resting and activated NK and CD8+T cells were found to express high levels of the two isoforms of c-FLIP. Small interference RNA-mediated inhibition of c-FLIP expression in NK cells abrogated their resistance to the apoptotic effect of soluble TRAIL. Thus, once activated the major cytotoxic effector cells are potentially sensitive to TRAIL, but are physiologically protected to its apoptotic action by intracellular level of c-FLIP. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Killer cells protect themselves Michael Bennett Blood 2004 104: 2214. [Full Text] [PDF] This article has been cited by other articles: G. Gobbi, P. Mirandola, C. Carubbi, C. Micheloni, C. Malinverno, P. Lunghi, A. Bonati, and M. Vitale Phorbol ester-induced PKC{epsilon} down-modulation sensitizes AML cells to TRAIL-induced apoptosis and cell differentiation Blood, March 26, 2009; 113(13): 3080 - 3087. [Abstract] [Full Text] [PDF] B. Berent-Maoz, A. M. Piliponsky, I. Daigle, H.-U. Simon, and F. Levi-Schaffer Human Mast Cells Undergo TRAIL-Induced Apoptosis J. Immunol., February 15, 2006; 176(4): 2272 - 2278. [Abstract] [Full Text] [PDF] K. Sato, A. Niessner, S. L. Kopecky, R. L. Frye, J. J. Goronzy, and C. M. Weyand TRAIL-expressing T cells induce apoptosis of vascular smooth muscle cells in the atherosclerotic plaque J. Exp. Med., January 23, 2006; 203(1): 239 - 250. [Abstract] [Full Text] [PDF] N Arbour, E Rastikerdar, E McCrea, Y Lapierre, J Dorr, A Bar-Or, and J P Antel Upregulation of TRAIL expression on human T lymphocytes by interferon b and glatiramer acetate Multiple Sclerosis, December 1, 2005; 11(6): 652 - 657. [Abstract] [PDF] S. Skov, M. T. Pedersen, L. Andresen, P. Thor Straten, A. Woetmann, and N. Odum Cancer Cells Become Susceptible to Natural Killer Cell Killing after Exposure to Histone Deacetylase Inhibitors Due to Glycogen Synthase Kinase-3-Dependent Expression of MHC Class I-Related Chain A and B Cancer Res., December 1, 2005; 65(23): 11136 - 11145. [Abstract] [Full Text] [PDF]

	Copyright © 2004 by American Society of Hematology         Online ISSN: 1528-0020