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Blood, 1 November 2007, Vol. 110, No. 9, pp. 3480-3488. Prepublished online as a Blood First Edition Paper on July 2, 2007; DOI 10.1182/blood-2007-05-087940. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-05-087940v1 110/9/3480    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Taylor, P. A. Articles by Blazar, B. R. Search for Related Content PubMed PubMed Citation Articles by Taylor, P. A. Articles by Blazar, B. R. Related Collections Immunobiology Transplantation Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents TRANSPLANTATION Insights into the mechanism of FTY720 and compatibility with regulatory T cells for the inhibition of graft-versus-host disease (GVHD) Patricia A. Taylor1, Michael J. Ehrhardt1, Christopher J. Lees1, Jakub Tolar1, Brenda J. Weigel1, Angela Panoskaltsis-Mortari1, Jonathan S. Serody2, Volker Brinkmann3, and Bruce R. Blazar1 1 Division of Blood and Marrow Transplantation (BMT), University of Minnesota Cancer Center and Department of Pediatrics, Minneapolis, MN; 2 Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill; 3 Transplantation and Immunology, Novartis Institutes for BioMedical Research, Basel, Switzerland The immunomodulator FTY720 (FTY) has been shown to be beneficial in experimental models of organ transplantation and autoimmunity. We show that FTY significantly inhibited but did not prevent graft-versus-host disease (GVHD) in lethally irradiated or nonirradiated allogeneic recipients. Although most studies implicate prevention of lymphocyte egress from lymphoid organs as the primary mechanism of action, our data indicate that FTY effects on the host are more likely to be responsible for GVHD inhibition. FTY reduced splenic CD11c+ cells by 50%, and similarly reduced CD4+ and CD8+ T-cell responder frequencies in the spleen early after transplantation. Imaging of GFP+ effectors indicated that FTY modified donor effector T-cell migration to secondary lymphoid organs, but did not uniformly trap T cells in lymph nodes or prevent early effector migration to GVHD parenchymal target organs. Administration of FTY only prior to transplantation inhibited GVHD, indicating that the primary function of FTY may be targeted to host cells. FTY was additive with regulatory T cells for GVHD inhibition. FTY slightly impaired but did not abrogate a graft-versus-leukemia (GVL) effect against C1498, a myeloid leukemia. Our data further define the mechanisms of action and provide insight as to the potential clinical uses of FTY in allogeneic bone marrow transplant recipients. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: FTY720 prevents GVHD: the host perspective Xue-Zhong Yu and Claudio Anasetti Blood 2007 110: 3094. [Full Text] [PDF]

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