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Blood, 15 August 2006, Vol. 108, No. 4, pp. 1291-1297. Prepublished online as a Blood First Edition Paper on April 20, 2006; DOI 10.1182/blood-2006-02-003996. This Article Full Text (PDF) All Versions of this Article: blood-2006-02-003996v1 108/4/1291    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 Rezvani, K. Articles by Barrett, A J. Search for Related Content PubMed PubMed Citation Articles by Rezvani, K. Articles by Barrett, A J. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 15, 2006 Accepted April 4, 2006 High donor Foxp3-positive regulatory T-cell (TREG) content is associated with a low risk of GVHD following HLA-matched allogeneic stem cell transplantation (SCT) Katayoun Rezvani*, Stephan Mielke, Mojgan Ahmadzadeh, Yasemin Kilical, Bipin N Savani, Josette Zeilah, Keyvan Keyvanfar, Aldemar Montero, Nancy Hensel, Roger Kurlander, and A John Barrett Stem Cell Allogeneic Transplantation Section,Hematology Branch,National Heart Lung & Blood Institute Department of Surgery, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD Department of Laboratory Medicine, National Institutes of Health (NIH), Bethesda, MD, USA * Corresponding author; email: rezvanik{at}nhlbi.nih.gov. Regulatory T-cells (TREGs)that constitutively express Foxp3 are instrumental to the maintenance of tolerance and may suppress graft-versus-host disease (GVHD) in man. To determine whether regulatory T-cells in allogeneic stem cell transplants (SCT) ameliorate GVHD after transplantation we quantitated the coexpression of Foxp3 on CD4+ T-cells in 32 donor SCT infused into HLA-matched siblings and examined GVHD incidence in respective recipients. High CD4+Foxp3+ T-cell count in the donor was associated with an reduced risk of GVHD. We monitored TREG during immune reconstitution in 21 patients with leukemia undergoing a T-cell depleted allogeneic SCT. Early post-SCT, there was a significant expansion in the CD4+Foxp3+ T-cell compartment. A low CD4+Foxp3+ T-cell count early post-SCT (day 30) was associated with an increased risk of GVHD and the ratio of CD4+Foxp3+ T-cells to CD4+CD25+Foxp3-T-cells was significantly reduced in patients with GVHD suggesting diminished control of effector T-cells. Our findings suggest that graft TREG content may predict for risk of GVHD post-SCT. Determining the TREG levels in the donor and manipulating TREGs early after transplantation may provide a new approach to controlling GVHD. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Donor Foxp3-positive T cells: the missing link Allan D. Hess Blood 2006 108: 1121-1122. [Full Text] This article has been cited by other articles: J. K. Davies, L. M. Nadler, and E. C. Guinan Expansion of Allospecific Regulatory T Cells After Anergized, Mismatched Bone Marrow Transplantation Science Translational Medicine, October 7, 2009; 1(1): 1ra3 - 1ra3. [Abstract] [Full Text] [PDF] 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] 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] B. Blanco, J. A. Perez-Simon, L. I. Sanchez-Abarca, T. Caballero-Velazquez, S. Gutierrez-Cossio, P. Hernandez-Campo, M. Diez-Campelo, C. Herrero-Sanchez, C. Rodriguez-Serrano, C. Santamaria, et al. Treatment with bortezomib of human CD4+ T cells preserves natural regulatory T cells and allows the emergence of a distinct suppressor T-cell population Haematologica, July 1, 2009; 94(7): 975 - 983. [Abstract] [Full Text] [PDF] O. Bohana-Kashtan, S. Morisot, R. Hildreth, C. Brayton, H. I. Levitsky, and C. I. Civin Selective Reduction of Graft-versus-Host Disease-Mediating Human T Cells by Ex Vivo Treatment with Soluble Fas Ligand J. Immunol., July 1, 2009; 183(1): 696 - 705. [Abstract] [Full Text] [PDF] M. Ahmadzadeh, A. Felipe-Silva, B. Heemskerk, D. J. Powell Jr, J. R. Wunderlich, M. J. Merino, and S. A. Rosenberg FOXP3 expression accurately defines the population of intratumoral regulatory T cells that selectively accumulate in metastatic melanoma lesions Blood, December 15, 2008; 112(13): 4953 - 4960. [Abstract] [Full Text] [PDF] E. Gatza, C. E. Rogers, S. G. Clouthier, K. P. Lowler, I. Tawara, C. Liu, P. Reddy, and J. L. M. Ferrara Extracorporeal photopheresis reverses experimental graft-versus-host disease through regulatory T cells Blood, August 15, 2008; 112(4): 1515 - 1521. [Abstract] [Full Text] [PDF] S. Mielke, R. Nunes, K. Rezvani, V. S. Fellowes, A. Venne, S. R. Solomon, Y. Fan, E. Gostick, D. A. Price, C. Scotto, et al. A clinical-scale selective allodepletion approach for the treatment of HLA-mismatched and matched donor-recipient pairs using expanded T lymphocytes as antigen-presenting cells and a TH9402-based photodepletion technique Blood, April 15, 2008; 111(8): 4392 - 4402. [Abstract] [Full Text] [PDF] X. Feng, S. Kajigaya, E. E. Solomou, K. Keyvanfar, X. Xu, N. Raghavachari, P. J. Munson, T. M. Herndon, J. Chen, and N. S. Young Rabbit ATG but not horse ATG promotes expansion of functional CD4+CD25highFOXP3+ regulatory T cells in vitro Blood, April 1, 2008; 111(7): 3675 - 3683. [Abstract] [Full Text] [PDF] D. Atanackovic, Y. Cao, T. Luetkens, J. Panse, C. Faltz, J. Arfsten, K. Bartels, C. Wolschke, T. Eiermann, A. R. Zander, et al. CD4+CD25+FOXP3+ T regulatory cells reconstitute and accumulate in the bone marrow of patients with multiple myeloma following allogeneic stem cell transplantation Haematologica, March 1, 2008; 93(3): 423 - 430. [Abstract] [Full Text] [PDF] A. J. Barrett Leukemia Vaccines to Boost the Graft-versus-Leukemia Effect after Allogeneic Stem Cell Transplantation ASCO Educational Book, January 1, 2008; 2008(1): 330 - 333. [Abstract] [Full Text] [PDF] E. E. Solomou, K. Rezvani, S. Mielke, D. Malide, K. Keyvanfar, V. Visconte, S. Kajigaya, A. J. Barrett, and N. S. Young Deficient CD4+ CD25+ FOXP3+ T regulatory cells in acquired aplastic anemia Blood, September 1, 2007; 110(5): 1603 - 1606. [Abstract] [Full Text] [PDF] S. Mielke, K. Rezvani, B. N. Savani, R. Nunes, A. S. M. Yong, J. Schindler, R. Kurlander, V. Ghetie, E. J. Read, S. R. Solomon, et al. Reconstitution of FOXP3+ regulatory T cells (Tregs) after CD25-depleted allotransplantion in elderly patients and association with acute graft-versus-host disease Blood, September 1, 2007; 110(5): 1689 - 1697. [Abstract] [Full Text] [PDF] C. Pabst, H. Schirutschke, G. Ehninger, M. Bornhauser, and U. Platzbecker The Graft Content of Donor T Cells Expressing {gamma}{delta}TCR+ and CD4+foxp3+ Predicts the Risk of Acute Graft versus Host Disease after Transplantation of Allogeneic Peripheral Blood Stem Cells from Unrelated Donors Clin. Cancer Res., May 15, 2007; 13(10): 2916 - 2922. [Abstract] [Full Text] [PDF] J. Chen, F. M. Ellison, M. A. Eckhaus, A. L. Smith, K. Keyvanfar, R. T. Calado, and N. S. Young Minor Antigen H60-Mediated Aplastic Anemia Is Ameliorated by Immunosuppression and the Infusion of Regulatory T Cells J. Immunol., April 1, 2007; 178(7): 4159 - 4168. [Abstract] [Full Text] [PDF]

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