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Blood, 1 November 2005, Vol. 106, No. 9, pp. 3300-3307. Prepublished online as a Blood First Edition Paper on July 7, 2005; DOI 10.1182/blood-2005-04-1632. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: 2005-04-1632v1 106/9/3300    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 Wysocki, C. A Articles by Serody, J. S Search for Related Content PubMed PubMed Citation Articles by Wysocki, C. A Articles by Serody, J. S Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 21, 2005 Accepted June 16, 2005 Critical role for CCR5 in the function of donor CD4+CD25+ regulatory T cells during acute graft-versus-host disease Christian A Wysocki, Qi Jiang, Angela Panoskaltsis-Mortari, Patricia A Taylor, Karen P McKinnon, Lishan Su, Bruce R Blazar, and Jonathan S Serody* Department of Microbiology and Immunology, and the Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Department of Pediatrics, Division of Pediatric Bone Marrow Transplantation and the University of Minnesota Cancer Center, University of Minnesota, Minneapolis, MN, USA Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Microbiology and Immunology, and the Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA * Corresponding author; email: jonathan_serody{at}med.unc.edu. CD4+CD25+ regulatory T cells (Treg) have been shown to inhibit graft-versus-host disease (GVHD) in murine models, and this suppression was mediated by Treg expressing the lymphoid homing molecule L-selectin. Here, we demonstrate that Treg lacking expression of the chemokine receptor CCR5 were far less effective in preventing lethality from GVHD. Survival of irradiated recipient animals given transplants supplemented with CCR50-/- Treg was significantly decreased, and GVHD scores were enhanced compared to animals receiving WT Treg. CCR5-/- T reg were functional in suppressing T cell proliferation in vitro and ex vivo. However, although the accumulation of Treg within lymphoid tissues during the first week after transplantation was not dependent on CCR5, the lack of function of CCR5-/- Treg correlated with impaired accumulation of these cells in the liver, lung, spleen and mesenteric lymph node, more than one week after transplant. These data are the first to definitively demonstrate a requirement for CCR5 in Treg function, and indicate that in addition to their previously defined role in inhibiting effector T cell expansion in lymphoid tissues during GVHD, later recruitment of Treg to both lymphoid tissues and GVHD target organs is important in their ability to prolong survival after allogeneic bone marrow transplantation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Socie and B. R. Blazar Acute graft-versus-host disease: from the bench to the bedside Blood, November 12, 2009; 114(20): 4327 - 4336. [Abstract] [Full Text] [PDF] A. M. Wolf, K. Eller, R. Zeiser, C. Durr, U. V. Gerlach, M. Sixt, L. Markut, G. Gastl, A. R. Rosenkranz, and D. Wolf The Sphingosine 1-Phosphate Receptor Agonist FTY720 Potently Inhibits Regulatory T Cell Proliferation In Vitro and In Vivo J. Immunol., September 15, 2009; 183(6): 3751 - 3760. 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