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Blood, 15 February 2006, Vol. 107, No. 4, pp. 1717-1723. Prepublished online as a Blood First Edition Paper on November 8, 2005; DOI 10.1182/blood-2005-06-2529. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-06-2529v1 107/4/1717    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 Rieger, K. Articles by Uharek, L. Search for Related Content PubMed PubMed Citation Articles by Rieger, K. Articles by Uharek, L. Related Collections Immunobiology Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Mucosal FOXP3+ regulatory T cells are numerically deficient in acute and chronic GvHD Kathrin Rieger, Christoph Loddenkemper, Jochem Maul, Thomas Fietz, Daniel Wolff, Harald Terpe, Beate Steiner, Erika Berg, Stephan Miehlke, Martin Bornhäuser, Thomas Schneider, Martin Zeitz, Harald Stein, Eckhard Thiel, Rainer Duchmann, and Lutz Uharek From the Medical Clinic III, Hematology, Oncology, and Transfusion Medicine, the Consultation and Reference Center for Lymph Node Pathology and Hematopathology-Institute for Pathology, and Medical Clinic I, Gastroenterology, Charité-University Medicine Berlin, Campus Benjamin Franklin, Berlin; the Division of Hematology and Oncology, and the Department of Pathology, University of Rostock, Rostock; and the Department of Gastroenterology and the Department of Hematology, University School of Medicine Dresden, Germany. CD4+CD25+ regulatory T cells (Tregs) control immune responses to self- and foreign antigens and play a pivotal role in autoimmune diseases, infectious and noninfectious inflammation, and graft rejection. Since recent experimental studies have indicated that Tregs were able to ameliorate graft-versus-host disease (GvHD), we analyzed the number of infiltrating Tregs in the intestinal mucosa as one site of GvH reactivity using immunoenzymatic labeling to enumerate FOXP3+ T cells in 95 intestinal biopsies from 49 allografted patients in comparison with healthy controls and patients with infectious inflammation. While patients with cytomegalovirus (CMV)-colitis or diverticulitis showed a concomitant increase of CD8+ effectors and Tregs, acute and chronic GvHD were characterized by the complete lack of a counter-regulation indicated by a FOXP3+/CD8+ T-cell ratio identical to healthy controls. In contrast, specimens without histologic signs of GvHD demonstrated increased numbers of FOXP3+ per CD8+ T cells, indicating that the potential for Treg expansion is principally maintained in allografted patients. Our findings provide evidence that GvHD is associated with an insufficient up-regulation of Tregs in intestinal GvHD lesions. The determination of FOXP3+/CD8+ ratio can be a helpful tool to discriminate GvHD from infectious inflammation after allogeneic stem cell transplantation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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] B. Blanco, J. A. Perez-Simon, L. I. Sanchez-Abarca, T. Caballero-Velazquez, S. 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Arrazi, S. Nicholls, P. Mahendra, C. Craddock, and P. A. H. Moss CXCL10-CXCR3 interactions play an important role in the pathogenesis of acute graft-versus-host disease in the skin following allogeneic stem-cell transplantation Blood, December 1, 2007; 110(12): 3827 - 3832. [Abstract] [Full Text] [PDF] X. Chen, S. Vodanovic-Jankovic, B. Johnson, M. Keller, R. Komorowski, and W. R. Drobyski Absence of regulatory T-cell control of TH1 and TH17 cells is responsible for the autoimmune-mediated pathology in chronic graft-versus-host disease Blood, November 15, 2007; 110(10): 3804 - 3813. [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]

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