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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 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 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 Ma, B. Y. Articles by Ochi, A. Search for Related Content PubMed PubMed Citation Articles by Ma, B. Y. Articles by Ochi, A. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY 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 From the University Health Network, Toronto, ON, Canada; Department of Immunology, University of Toronto, Toronto, ON, Canada; Department of Microbiology and Immunology, University of Western Ontario, London, ON, Canada; and Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. OX40 and 4-1BB are members of the tumor necrosis factor (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 we were investigating the expression of OX40 and 4-1BB on activated human T cells, we found that they colocalize. The study of receptor gene–transfected cells showed that both receptors coendocytose and the complex of OX40 and 4-1BB was detected by specific ligands or antibodies (Abs). The heterodimer of OX40 and 4-1BB was identified by sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE) under nonreduced conditions and was associated with the tumor receptor–associated factor (TRAF) family proteins in a unique manner. Furthermore, the stimulation of OX40/4-1BB rendered cells sensitive to apoptosis induced by TNF- that accompanied reduced activation of nuclear factor-B (NF-B). Finally, the OX40/4-1BB stimulation repressed the mitogen response in activated CD25+CD4+ T cells and preactivated 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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