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Blood, 6 August 2009, Vol. 114, No. 6, pp. 1263-1269. Prepublished online as a Blood First Edition Paper on May 13, 2009; DOI 10.1182/blood-2009-02-206730. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2009-02-206730v1 114/6/1263    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 Google Scholar Articles by Becker, C. Articles by Jonuleit, H. PubMed PubMed Citation Articles by Becker, C. Articles by Jonuleit, H. Related Collections Immunobiology Transplantation Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Protection from graft-versus-host disease by HIV-1 envelope protein gp120-mediated activation of human CD4+CD25+ regulatory T cells Christian Becker1, Christian Taube2, Tobias Bopp3, Christoph Becker4, Kai Michel1, Jan Kubach1, Sebastian Reuter2, Nina Dehzad2, Markus F. Neurath4, Kurt Reifenberg5, Franz-Joseph Schneider6, Edgar Schmitt3, and Helmut Jonuleit1 1 Department of Dermatology, 2 III Medical Department, 3 Institute of Immunology, 4 Institute of Molecular Medicine, and 5 Central Animal Facility, Johannes Gutenberg-University, Mainz; and 6 Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany Naturally occurring CD4+CD25+ regulatory T cells (Tregs) represent a unique T-cell lineage that is endowed with the ability to actively suppress immune responses. Therefore, approaches to modulate Treg function in vivo could provide ways to enhance or reduce immune responses and lead to novel therapies. Here we show that the CD4 binding human immunodeficiency virus-1 envelope glycoprotein gp120 is a useful and potent tool for functional activation of human Tregs in vitro and in vivo. Gp120 activates human Tregs by binding and signaling through CD4. Upon stimulation with gp120, human Tregs accumulate cyclic adenosine monophosphate (cAMP) in their cytosol. Inhibition of endogeneous cAMP synthesis prevents gp120-mediated Treg activation. Employing a xenogeneic graft versus host disease model that has been shown to be applicable for the functional analysis of human Tregs in vivo, we further show that a single dose of gp120 is sufficient to prevent lethal graft versus host disease and that the tolerizing effect of gp120 is strictly dependent on the presence of human Tregs and their up-regulation of cAMP upon gp120-mediated activation. Our findings demonstrate that stimulation via the CD4 receptor represents a T-cell receptor–independent Treg activating pathway with potential to induce immunologic tolerance in vivo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Waking up regulatory T cells Kjetil Taskén Blood 2009 114: 1136-1137. [Full Text] [PDF] This article has been cited by other articles: K. Tasken Waking up regulatory T cells Blood, August 6, 2009; 114(6): 1136 - 1137. [Full Text] [PDF]

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