SEARCH:   Advanced

Blood, 1 May 2008, Vol. 111, No. 9, pp. 4741-4751. Prepublished online as a Blood First Edition Paper on February 14, 2008; DOI 10.1182/blood-2007-10-115220. This Article Full Text Full Text (PDF) Supplemental Table and Figure All Versions of this Article: blood-2007-10-115220v1 111/9/4741    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 CrossRef Google Scholar Articles by Pichler, K. Articles by Grassmann, R. PubMed PubMed Citation Articles by Pichler, K. Articles by Grassmann, R. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Strong induction of 4-1BB, a growth and survival promoting costimulatory receptor, in HTLV-1–infected cultured and patients' T cells by the viral Tax oncoprotein Klemens Pichler1, Tarek Kattan2, Juliane Gentzsch1, Andrea K. Kress1, Graham P. Taylor3, Charles R. M. Bangham2, and Ralph Grassmann1 1 Institute of Clinical and Molecular Virology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany; 2 Department of Immunology, Wright-Fleming Institute, Imperial College, London, United Kingdom; and 3 Department of Genito-Urinary Medicine, Imperial College, London, United Kingdom Human T-cell leukemia virus type 1 (HTLV-1), the cause of adult T-cell leukemia, stimulates the growth of infected T cells in cultures and in nonleukemic patients. In the latter, HTLV-1 is found in long-term persisting T-cell clones. The persistence of normal T cells is controlled by the growth-stimulating and antiapoptotic functions of costimulatory receptors, while the growth-stimulating HTLV-1 functions are mediated by the viral oncoprotein Tax. Here we analyzed the impact of Tax on costimulatory receptors in T cells with repressible Tax and found that among these receptors 4-1BB (TNFRSF9/CD137/ILA) was induced most strongly. Up-regulated 4-1BB expression was a consistent feature of all HTLV-1–infected cell lines, whether patient-derived or in vitro transformed. Tax was sufficient to induce the expression of the endogenous 4-1BB gene in uninfected T cells, and it strongly activated (45-fold) the 4-1BB promoter via a single NF-B site. The ligand of 4-1BB was also found on transformed T-cell lines, opening up the possibility of autostimulation. Moreover, 4-1BB expression in patients' lymphocytes ex vivo correlated with Tax expression, strongly suggesting Tax-mediated 4-1BB activation in vivo. Thus, 4-1BB up-regulation by Tax could contribute to growth, survival, and clonal expansion of the infected cells during persistence and disease. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020