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Blood, 15 March 2007, Vol. 109, No. 6, pp. 2649-2656. Prepublished online as a Blood First Edition Paper on November 9, 2006; DOI 10.1182/blood-2006-08-044529. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-08-044529v1 109/6/2649    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 Nguyen, V. H. Articles by Negrin, R. S. Search for Related Content PubMed PubMed Citation Articles by Nguyen, V. H. Articles by Negrin, R. S. Related Collections Immunobiology Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION In vivo dynamics of regulatory T-cell trafficking and survival predict effective strategies to control graft-versus-host disease following allogeneic transplantation Vu H. Nguyen1, Robert Zeiser1, Daniel L. daSilva1, Daisy S. Chang1, Andreas Beilhack1, Christopher H. Contag2, and Robert S. Negrin1 1 Department of Medicine, Division of Bone Marrow Transplantation, Stanford University, Stanford, CA; 2 Departments of Pediatrics, Radiology, and Microbiology & Immunology, Stanford University, Stanford, CA CD4+CD25+ regulatory T cells (Tregs) suppress immune responses to alloantigens. The in vivo circulation and tissue localization of Tregs during an adaptive immune response remain unclear. We noninvasively tracked luciferase-expressing Tregs over time in an allogeneic bone marrow transplant model and demonstrated colocalization with effector T cells and initial expansion in secondary lymphoid organs before migration into inflamed tissues. Inflammation induced by irradiation and the allogeneic setting provided crucial stimuli for early Treg expansion and migration, leading to parallel reduction of effector T-cell proliferation in lymphoid organs and peripheral tissues. Treg transplants conferred long-term protection from systemic inflammatory challenge consistent with Treg in vivo survival. Suppression occurred during multiple phases of inflammation, but is optimal in the initial phase, providing protection from graft-versus-host disease while maintaining the graft-versus-tumor effect even at physiologic doses of Tregs due to their in vivo expansion, hence overcoming a major barrier to potential clinical applications of Tregs given their rarity. 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Bestard, J. M. Cruzado, M. Mestre, A. Caldes, J. Bas, M. Carrera, J. Torras, I. Rama, F. Moreso, D. Seron, et al. Achieving Donor-Specific Hyporesponsiveness Is Associated with FOXP3+ Regulatory T Cell Recruitment in Human Renal Allograft Infiltrates J. Immunol., October 1, 2007; 179(7): 4901 - 4909. [Abstract] [Full Text] [PDF] R. Zeiser, V. H. Nguyen, J.-Z. Hou, A. Beilhack, E. Zambricki, M. Buess, C. H. Contag, and R. S. Negrin Early CD30 signaling is critical for adoptively transferred CD4+CD25+ regulatory T cells in prevention of acute graft-versus-host disease Blood, March 1, 2007; 109(5): 2225 - 2233. [Abstract] [Full Text] [PDF]

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