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Blood, 15 March 2004, Vol. 103, No. 6, pp. 2410-2416. Prepublished online as a Blood First Edition Paper on November 6, 2003; DOI 10.1182/blood-2003-06-2073. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-06-2073v1 103/6/2410    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 Clark, F. J. Articles by Chakraverty, R. Search for Related Content PubMed PubMed Citation Articles by Clark, F. J. Articles by Chakraverty, R. Related Collections Immunobiology Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Chronic graft-versus-host disease is associated with increased numbers of peripheral blood CD4+CD25high regulatory T cells Fiona J. Clark, Richard Gregg, Karen Piper, Debbie Dunnion, Lisa Freeman, Mike Griffiths, Gulnaz Begum, Premini Mahendra, Charles Craddock, Paul Moss, and Ronjon Chakraverty From the Department of Hematology, Institute of Cancer Studies, University of Birmingham, Edgbaston, Birmingham, United Kingdom; Regional Genetics Laboratory, Birmingham Women's Hospital, Birmingham, United Kingdom; Cancer Research United Kingdom Clinical Trials Unit, University of Birmingham, Birmingham, United Kingdom. Chronic graft-versus-host disease (cGVHD) is characterized by a state of profound immunodeficiency in association with alloreactive and autoimmune phenomena. These observations indicate an impairment of immunologic tolerance that could involve both central and peripheral mechanisms. Defective thymic function may contribute to dysregulation of central tolerance, but few studies have addressed peripheral tolerance. Recently a population of CD4+CD25+ T cells (Treg cells) has been characterized, which controls immunologic reactivity in vivo and which on transfer can prevent experimental acute GVHD. We investigated the number and function of peripheral blood CD4+CD25high T cells in patients more than 100 days after allogeneic hematopoietic stem cell transplantation. Patients with cGVHD had markedly elevated numbers of CD4+CD25high T cells as compared to patients without GVHD. CD4+CD25high T cells derived from patients in both groups were of donor origin, lacked markers of recent activation, and expressed intracellular CD152. In contrast to controls, CD4+CD25high T cells derived from patients with cGVHD were characterized by lower surface CD62L expression. In vitro, CD4+CD25high T cells were hyporesponsive to polyclonal stimulation and suppressed the proliferation and cytokine synthesis of CD4+CD25- cells, an effect that was independent of interleukin 10. These results indicate that chronic graft-versus-host injury does not occur as a result of Treg cell deficiency. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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] R. Kapur, S. Ebeling, and A. Hagenbeek B-cell involvement in chronic graft-versus-host disease Haematologica, November 1, 2008; 93(11): 1702 - 1711. [Abstract] [Full Text] [PDF] L. Codarri, L. Vallotton, D. Ciuffreda, J.-P. Venetz, M. Garcia, K. Hadaya, L. Buhler, S. Rotman, M. Pascual, and G. Pantaleo Expansion and tissue infiltration of an allospecific CD4+CD25+CD45RO+IL-7R{alpha}high cell population in solid organ transplant recipients J. Exp. Med., July 9, 2007; 204(7): 1533 - 1541. [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] C. Fozza, E. Nadal, M. Longinotti, and F. Dazzi T-cell receptor repertoire usage after allografting differs between CD4+CD25+ regulatory T cells and their CD4+CD25 counterpart Haematologica, February 1, 2007; 92(2): 206 - 214. [Abstract] [Full Text] [PDF] T. Mutis, R. S. van Rijn, E. R. Simonetti, T. Aarts-Riemens, M. E. Emmelot, L. van Bloois, A. Martens, L. F. Verdonck, and S. B. Ebeling Human Regulatory T Cells Control Xenogeneic Graft-versus-Host Disease Induced by Autologous T Cells in RAG2-/-{gamma}c-/- Immunodeficient Mice. Clin. Cancer Res., September 15, 2006; 12(18): 5520 - 5525. [Abstract] [Full Text] [PDF] K. Rezvani, S. Mielke, M. Ahmadzadeh, Y. Kilical, B. N. Savani, J. Zeilah, K. Keyvanfar, A. Montero, N. Hensel, R. Kurlander, et al. High donor FOXP3-positive regulatory T-cell (Treg) content is associated with a low risk of GVHD following HLA-matched allogeneic SCT Blood, August 15, 2006; 108(4): 1291 - 1297. [Abstract] [Full Text] [PDF] M. Miyara, Z. Amoura, C. Parizot, C. Badoual, K. Dorgham, S. Trad, M. 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Reduced frequency of FOXP3+ CD4+CD25+ regulatory T cells in patients with chronic graft-versus-host disease Blood, October 15, 2005; 106(8): 2903 - 2911. [Abstract] [Full Text] [PDF] S. J. Lee New approaches for preventing and treating chronic graft-versus-host disease Blood, June 1, 2005; 105(11): 4200 - 4206. [Abstract] [Full Text] [PDF] Y. Miura, C. J. Thoburn, E. C. Bright, M. L. Phelps, T. Shin, E. C. Matsui, W. H. Matsui, S. Arai, E. J. Fuchs, G. B. Vogelsang, et al. Association of Foxp3 regulatory gene expression with graft-versus-host disease Blood, October 1, 2004; 104(7): 2187 - 2193. [Abstract] [Full Text] [PDF] K. V. Komanduri and R. E. Champlin GVHD therapy: the best-laid schemes... Blood, September 1, 2004; 104(5): 1240 - 1241. [Full Text] [PDF]

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