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Blood, 1 July 2006, Vol. 108, No. 1, pp. 390-399. Prepublished online as a Blood First Edition Paper on March 7, 2006; DOI 10.1182/blood-2006-01-0329. This Article Full Text (PDF) All Versions of this Article: 2006-01-0329v1 108/1/390    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 Zeiser, R. S Articles by Negrin, R. S Search for Related Content PubMed PubMed Citation Articles by Zeiser, R. S Articles by Negrin, R. S Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 25, 2006 Accepted February 24, 2006 Inhibition of CD4+CD25+ regulatory T cell function by calcineurin dependent interleukin-2 production Robert S Zeiser, Vu H Nguyen, Andreas Beilhack, Martin Buess, Stephan Schulz, Jeanette Baker, Christopher H Contag, and Robert S Negrin* Division of Bone Marrow Transplantation, Department of Medicine, Stanford University, Stanford, CA, USA; Division of Hematology and Oncology, Department of Medicine, Freiburg University, Freiburg, Germany Division of Bone Marrow Transplantation, Department of Medicine, Stanford University, Stanford, CA, USA Division of Biochemistry, Department of Medicine, Stanford University, Stanford, CA, USA Department of Pathology, Technische Universitat Munchen, Munich, Germany Division of Pediatrics / Microbiology & Immunology, Department of Medicine, Stanford University, Stanford, CA, USA * Corresponding author; email: negrs{at}stanford.edu. CD4+CD25+ regulatory T (Treg) cells control immunological tolerance and anti-tumor immune responses. Therefore, in vivo modification of Treg function by immunosuppressant drugs has broad implications for transplantation biology, autoimmunity and vaccination strategies. In vivo bioluminescence imaging demonstrated reduced early proliferation of donor derived luciferase-labeled conventional T-cells in animals treated with Treg after major MHC mismatch bone marrow transplantation. Combining Treg with Cyclosporine A (CSA), but not Rapamycin (RAPA) or Mycophenolate mofetil (MMF) suppressed Treg function assessed by increased T cell proliferation, graft-versus-host-disease (GVHD) severity and reduced survival. Expansion of Treg and FoxP3 expression within this population was lowest in conjunction with CSA suggesting calcineurin dependent interleukin (IL)-2 production to be critically required for Treg in vivo. The functional defect of Treg after CSA exposure could be reversed by exogenous IL-2. Further the Treg/RAPA combination preserved graft-versus-tumor (GVT) effector function against leukemia cells. Our data indicate that RAPA and MMF rather than CSA preserve function of Treg in pathological immune responses such as GVHD without weakening the GVT effect. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. M. Wolf, K. Eller, R. Zeiser, C. Durr, U. V. Gerlach, M. Sixt, L. Markut, G. Gastl, A. R. Rosenkranz, and D. Wolf The Sphingosine 1-Phosphate Receptor Agonist FTY720 Potently Inhibits Regulatory T Cell Proliferation In Vitro and In Vivo J. Immunol., September 15, 2009; 183(6): 3751 - 3760. [Abstract] [Full Text] [PDF] Z. Zeng, Y. Xi Shi, I. J. Samudio, R.-Y. Wang, X. Ling, O. Frolova, M. Levis, J. B. Rubin, R. R. Negrin, E. H. Estey, et al. 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