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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 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 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 Zeiser, R. Articles by Negrin, R. S. Search for Related Content PubMed PubMed Citation Articles by Zeiser, R. Articles by Negrin, R. S. Related Collections Immunobiology Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Inhibition of CD4+CD25+ regulatory T-cell function by calcineurin-dependent interleukin-2 production Robert Zeiser, Vu H. Nguyen, Andreas Beilhack, Martin Buess, Stephan Schulz, Jeanette Baker, Christopher H. Contag, and Robert S. Negrin From the Division of Bone Marrow Transplantation, Department of Medicine, Stanford University, Stanford, CA; Division of Hematology and Oncology, Department of Medicine, Freiburg University Medical Center, Freiburg, Germany; Division of Biochemistry, Department of Medicine, Stanford University, Stanford, CA; Department of Pathology, Technische Universität München, München, Germany; and Division of Pediatrics/Microbiology and Immunology, Department of Medicine, Stanford University, Stanford, CA. CD4+CD25+ regulatory T (Treg) cells control immunologic tolerance and antitumor 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 cells after major histocompatibility complex mismatch bone marrow transplantation. Combining Treg cells 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 that calcineurin-dependent interleukin 2 (IL-2) production is critically required for Treg cells in vivo. The functional defect of Treg cells after CSA exposure could be reversed by exogenous IL-2. Further, the Treg plus 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 cells in pathologic immune responses such as GVHD without weakening the GVT effect. (Blood. 2006;108:390-399) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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. Targeting the leukemia microenvironment by CXCR4 inhibition overcomes resistance to kinase inhibitors and chemotherapy in AML Blood, June 11, 2009; 113(24): 6215 - 6224. [Abstract] [Full Text] [PDF] A. Valle, T. Jofra, A. Stabilini, M. Atkinson, M.-G. Roncarolo, and M. 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