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Blood, 15 November 2008, Vol. 112, No. 10, pp. 4328-4336. Prepublished online as a Blood First Edition Paper on September 9, 2008; DOI 10.1182/blood-2008-03-146662. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-03-146662v1 112/10/4328    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 Beyersdorf, N. Articles by Hunig, T. Search for Related Content PubMed PubMed Citation Articles by Beyersdorf, N. Articles by Hunig, T. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 21, 2008 Accepted August 7, 2008 Protection from graft versus host disease with a novel B7 binding site-specific mouse anti-mouse CD28 mAb Niklas Beyersdorf*, Xin Ding, Gregor Blank, Kevin M Dennehy, Thomas Kerkau, and Thomas Hunig Institute for Virology and Immunobiology, University of Wurzburg, Wurzburg, Germany * Corresponding author; email: niklas.beyersdorf{at}vim.uni-wuerzburg.de. We studied the role of CD28 in T cell biology and T cell-mediated pathology using a novel mouse anti-mouse CD28 antibody, E18, which recognizes an epitope close to the B7 binding site. In vitro, this antibody completely blocked binding of B7 molecules to CD28 expressed on mouse thymocytes, but enhanced anti-CD3-induced proliferation of peripheral T cells. Injections of E18 monoclonal antibody (mAb) into normal BALB/c mice in vivo, however, led to a reversible reduction in Treg cell frequencies among CD4+ cells, both in the thymus and in secondary lymphoid organs, suggesting that E18 acted as an inhibitor of CD28 signaling under these conditions. Antagonistic activity of E18 in vivo was further implied by suppressed responses of conventional CD4+ T cells to stimulation with the superantigen staphylococcal enterotoxin B and in a model of acute graft versus host disease (aGvHD). In contrast to healthy mice, intact mAb E18, but not its non-stimulatory Fab fragment, increased the frequencies of Treg cells among CD4+ T cells in these pro-inflammatory settings allowing for efficacious protection from aGvHD. Thus, the agonistic signal generated by conventional, i.e. non-superagonistic, anti-CD28 antibodies is important for their immunotherapeutic potential in vivo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C.-H. Hsieh, J.-T. Hsu, Y.-C. Hsieh, M. Frink, R. Raju, W. J. Hubbard, K. I. Bland, and I. H. Chaudry Suppression of Activation and Costimulatory Signaling in Splenic CD4+ T Cells after Trauma-Hemorrhage Reduces T-Cell Function: A Mechanism of Post-Traumatic Immune Suppression Am. J. Pathol., October 1, 2009; 175(4): 1504 - 1514. [Abstract] [Full Text] [PDF]

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