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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 (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 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 Social Bookmarking                   What's this? Submitted August 21, 2002 Accepted December 15, 2002 CD28 loss in senescent CD4+ T cells: reversal by interleukin-12 stimulation Kenneth J Warrington, Abbe N Vallejo, Cornelia M Weyand, and Jorg J Goronzy* Departments of Medicine and Immunology, Mayo Clinic, Rochester, MN, USA * Corresponding author; email: goronzy.jorg{at}mayo.edu. 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-, due to an inoperative CD28 initiator element. It is currently unknown whether CD28 loss is irreversible. The present study examined cytokines for their ability to re-induce CD28 expression. CD4+CD28null T cells constitutively expressed interleukin (IL)-12 and receptors, which were functional and allowed for the upregulation of the STAT-4-dependent gene, CD161. Co-stimulation of the T-cell and IL-12 receptors induced the transcription of CD28 in ~50% of CD4+CD28null T-cell clones and lines. IL-12 by itself did not restore CD28 expression. Upregulation of CD28 after IL-12 exposure correlated with the re-assembly 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. 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. Kaski CD4+CD28null T cells in coronary artery disease: when helpers become killers Cardiovasc Res, January 1, 2009; 81(1): 11 - 19. 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