SEARCH:   Advanced

Blood, 15 March 2008, Vol. 111, No. 6, pp. 3257-3265. Prepublished online as a Blood First Edition Paper on December 12, 2007; DOI 10.1182/blood-2007-06-096081. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-06-096081v1 111/6/3257    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 Google Scholar Articles by Jasperson, L. K. Articles by Blazar, B. R. PubMed PubMed Citation Articles by Jasperson, L. K. Articles by Blazar, B. R. Related Collections Transplantation Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Indoleamine 2,3-dioxygenase is a critical regulator of acute graft-versus-host disease lethality Lisa K. Jasperson1, Christoph Bucher1, Angela Panoskaltsis-Mortari1, Patricia A. Taylor1, Andrew L. Mellor2, David H. Munn2, and Bruce R. Blazar1 1 University of Minnesota Cancer Center and Department of Pediatrics, Division of Bone Marrow Transplantation, Minneapolis, MN; and 2 Medical College of Georgia, Immunotherapy Center, Augusta, GA Graft-versus-host disease (GVHD) is initiated after activation of donor T cells by host antigen-presenting cells (APCs). The immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO) is expressed by APCs and parenchymal cells and is further inducible by inflammation. We investigated whether lethal conditioning and GVHD induce IDO and if IDO prevents tissue injury by suppressing immune responses at the induction site. We determined that IDO is a critical regulator of GVHD, most strikingly in the colon, where epithelial cells dramatically up-regulated IDO expression during GVHD. IDO–/– mice died more quickly from GVHD, displaying increased colonic inflammation and T-cell infiltration. GVHD protection was not mediated by control of T-cell proliferation, apoptosis, or effector mechanisms in lymphoid organs, nor did it require donor T regulatory cells. Instead, T cells in IDO–/– colons underwent increased proliferation and decreased apoptosis compared with their wild-type counterparts. This evidence suggests that IDO can act at the site of expression to decrease T-cell proliferation and survival, diminishing colonic inflammation and reducing disease severity. These studies are the first to identify a function for IDO in GVHD lethality and indicate that modulation of the IDO pathway may be an effective strategy for treatment of this disease. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: More ADO about IDO: GVHD Antonio Curti, Sara Trabanelli, and Roberto M. Lemoli Blood 2008 111: 2950. [Full Text] [PDF]

	Blood Online is supported in part by Genentech BioOncology and Biogen Idec
	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020