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Prepublished online as a Blood First Edition Paper on December 27, 2002; DOI 10.1182/blood-2002-08-2574. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-08-2574v1 101/9/3543    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 Warrington, K. J. Articles by Goronzy, J. J. Search for Related Content PubMed PubMed Citation Articles by Warrington, K. J. Articles by Goronzy, J. J. Related Collections Immunobiology Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 May 2003, Vol. 101, No. 9, pp. 3543-3549 IMMUNOBIOLOGY CD28 loss in senescent CD4+ T cells: reversal by interleukin-12 stimulation Kenneth J. Warrington, Abbe N. Vallejo, Cornelia M. Weyand, and Jörg J. Goronzy From the Departments of Medicine and Immunology, Mayo Clinic, Rochester, MN. CD28 is the quintessential costimulatory molecule expressed on CD4+ and CD8+ T cells. During chronic infections and the normal aging process, CD28 expression is lost, compromising the functional activity of T cells. CD28 loss is promoted by replicative stress, particularly in the presence of tumor necrosis factor-, owing to an inoperative CD28 initiator element. It is currently unknown whether CD28 loss is irreversible. The present study examined cytokines for their ability to reinduce CD28 expression. CD4+CD28null T cells constitutively expressed interleukin-12 (IL-12)  and  receptors, which were functional and allowed for the up-regulation of the signal transducer and activator of transcription-4 (STAT-4)-dependent gene CD161. Costimulation of the T-cell and IL-12 receptors induced the transcription of CD28 in approximately 50% of CD4+CD28null T-cell clones and lines. IL-12 by itself did not restore CD28 expression. Up-regulation of CD28 after IL-12 exposure correlated with the reassembly of the CD28-initiator protein complex. The re-expressed CD28 was functional and restored the ability of CD4+CD28null T cells to express CD25 and CD40 ligand. Our data suggest that IL-12 may, in part, functionally rescue senescent CD4+ T cells. © 2003 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: I. E. Dumitriu, E. T. Araguas, C. Baboonian, and J. C. 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