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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 (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 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. Social Bookmarking                   What's this? Submitted June 25, 2003 Accepted October 23, 2003 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 A Moss, and Ronjon Chakraverty* Department of Hematology, Institute for Cancer Studies, University of Birmingham, Birmingham, United Kingdom Regional Genetics Laboratory, Birmingham Women's Hospital, Birmingham, United Kingdom Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, United Kingdom * Corresponding author; email: Ronjon.Chakraverty{at}tbrc.mgh.harvard.edu. 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 immunological tolerance which 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) has been characterized which controls immunological reactivity in vivo and which upon transfer can prevent experimental acute GVHD. We investigated the number and function of peripheral blood CD4+CD25high T-cells in patients who were >100 days post-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 cGVHD patients were characterized by lower surface CD62L expression. In vitro, CD4+CD25high T-cells were hypo-responsive to polyclonal stimulation and suppressed the proliferation and cytokine synthesis of CD4+CD25- cells, an effect that was independent of IL-10. These results indicate that chronic graft-versus-host injury does not occur as a result of Treg 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. 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