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Blood, 15 September 2005, Vol. 106, No. 6, pp. 2002-2010. Prepublished online as a Blood First Edition Paper on June 7, 2005; DOI 10.1182/blood-2004-04-1622. This Article Full Text (PDF) All Versions of this Article: 2004-04-1622v1 106/6/2002    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 Ma, B. Y Articles by Ochi, A. Search for Related Content PubMed PubMed Citation Articles by Ma, B. Y Articles by Ochi, A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 28, 2004 Accepted May 11, 2005 The expression and the regulatory role of OX40 and 4-1BB heterodimer in activated human T cells Bruce Y Ma, Sebastian A Mikolajczak, Ali Danesh, Karoline A Hosiawa, Cheryl M Cameron, Akifumi Takaori-Kondo, Takashi Uchiyama, David J Kelvin, and Atsuo Ochi* Department of Biological Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan Department of Microbiology and Immunology, University Health Network, Toronto, Ontario, Canada Department of Microbiology and Immunology, University Health Network, Toronto, Ontario, Canada; Department of Immunology, University of Toronto, Toronto, Ontario, Canada Department of Microbiology and Immunology, University Health Network, Toronto, Ontario, Canada; Department of Microbiology and Immunology, The University of Western Ontario, London, Ontario, Canada The University of Western Ontario, Graduate School of Medicine, Kyoto University, Kyoto, Japan * Corresponding author; email: aochi{at}uhnresearch.ca. OX40 and 4-1BB are members of TNF family of costimulatory receptors whose signaling is important for differential immune responses mediated by CD4+ or CD8+ T cells. Although activated T cells may acquire OX40/4-1BB double positive phenotype and signaling from each receptor is expected to influence cell functions, the relevance between OX40 and 4-1BB has never been investigated before. While investigating the expression of OX40 and 4-1BB on activated human T cells we have found that they colocalize. The study of receptor gene-transfected cells showed that both receptor coendocytose and the complex of OX40 and 4-1BB was detectable by specific ligands or Abs. The heterodimer of OX40 and 4-1BB was identified by SDS-PAGE under nonreduced condition and found to associate with TRAF family proteins in a unique manner. Furthermore, the stimulation of OX40/4-1BB rendered cells sensitive to TNF- induced apoptosis that accompanied reduced activation of NF-B. Finally, the OX40/4-1BB stimulation repressed the mitogen response by activation induced CD25+CD4+ T cells and pre-activated CD8+ T cells. Thus, the OX40/4-1BB heterodimer appears to represent a unique regulatory receptor in activated T cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. W. Wlodarski, Z. Nearman, A. Jankowska, N. Babel, J. Powers, P. Leahy, H.-D. Volk, and J. P. Maciejewski Phenotypic differences between healthy effector CTL and leukemic LGL cells support the notion of antigen-triggered clonal transformation in T-LGL leukemia J. Leukoc. Biol., March 1, 2008; 83(3): 589 - 601. [Abstract] [Full Text] [PDF] S.-W. Lee, Y. Park, A. Song, H. Cheroutre, B. S. Kwon, and M. Croft Functional Dichotomy between OX40 and 4-1BB in Modulating Effector CD8 T Cell Responses J. Immunol., October 1, 2006; 177(7): 4464 - 4472. [Abstract] [Full Text] [PDF]

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