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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 (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 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 Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 30, 2006 Accepted October 30, 2006 In vivo dynamics of regulatory T cell trafficking and survival predict effective strategies to control graft-versus-host disease following allogeneic transplantation Vu H Nguyen*, Robert Zeiser, Daniel L daSilva, Daisy S Chang, Andreas Beilhack, Christopher H Contag, and Robert S Negrin Stanford University * Corresponding author; email: vunguyen{at}stanford.edu. CD4+CD25+ regulatory T cells (Treg) suppress immune responses to alloantigens. The in vivo circulation and tissue localization of Treg during an adaptive immune response remain unclear. We noninvasively tracked luciferase-expressing Treg over time in an allogeneic bone marrow transplant model and demonstrated co-localization 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 Treg due to their in vivo expansion, hence overcoming a major barrier to potential clinical applications of Treg given their rarity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y. Xie, M. Wu, R. Song, J. Ma, Y. Shi, W. Qin, and Y. Jin A glucocorticoid amplifies IL-2-induced selective expansion of CD4+CD25+FOXP3+ regulatory T cells in vivo and suppresses graft-versus-host disease after allogeneic lymphocyte transplantation Acta Biochim Biophys Sin, September 1, 2009; 41(9): 781 - 791. [Abstract] [Full Text] [PDF] X. Chen, R. Das, R. Komorowski, A. Beres, M. J. Hessner, M. Mihara, and W. R. Drobyski Blockade of interleukin-6 signaling augments regulatory T-cell reconstitution and attenuates the severity of graft-versus-host disease Blood, July 23, 2009; 114(4): 891 - 900. [Abstract] [Full Text] [PDF] K. Matthews, Z. Lim, B. Afzali, L. Pearce, A. Abdallah, S. Kordasti, A. Pagliuca, G. Lombardi, J. A. Madrigal, G. J. Mufti, et al. Imbalance of effector and regulatory CD4 T cells is associated with graft-versus-host disease after hematopoietic stem cell transplantation using a reduced intensity conditioning regimen and alemtuzumab Haematologica, July 1, 2009; 94(7): 956 - 966. [Abstract] [Full Text] [PDF] D. Zhao, C. Zhang, T. Yi, C.-L. Lin, I. Todorov, F. Kandeel, S. Forman, and D. Zeng In vivo-activated CD103+CD4+ regulatory T cells ameliorate ongoing chronic graft-versus-host disease Blood, September 1, 2008; 112(5): 2129 - 2138. [Abstract] [Full Text] [PDF] E. J. Akins and P. Dubey Noninvasive Imaging of Cell-Mediated Therapy for Treatment of Cancer J. Nucl. Med., June 1, 2008; 49(Suppl_2): 180S - 195S. [Abstract] [Full Text] [PDF] V. H. Nguyen, S. Shashidhar, D. S. Chang, L. Ho, N. Kambham, M. Bachmann, J. M. Brown, and R. S. Negrin The impact of regulatory T cells on T-cell immunity following hematopoietic cell transplantation Blood, January 15, 2008; 111(2): 945 - 953. [Abstract] [Full Text] [PDF] O. 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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