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Blood, 9 April 2009, Vol. 113, No. 15, pp. 3612-3619. Prepublished online as a Blood First Edition Paper on February 10, 2009; DOI 10.1182/blood-2008-07-168419. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-07-168419v1 113/15/3612    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 Wang, H. Articles by Yang, Y.-G. Search for Related Content PubMed PubMed Citation Articles by Wang, H. Articles by Yang, Y.-G. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 15, 2008 Accepted January 30, 2009 Paradoxical effects of IFN- in graft-vs.-host (GVH) disease reflect promotion of lymphohematopoietic GVH reactions and inhibition of epithelial tissue injury Hui Wang, Wannee Asavaroengchai, Beow Yong Yeap, Min-Guang Wang, Shumei Wang, Megan Sykes, and Yong-Guang Yang* Bone Marrow Transplantation Section, Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States Lower Columbia Pathologists, Longview, WA, United States * Corresponding author; email: yongguang.yang{at}tbrc.mgh.harvard.edu. IFN- has been shown to inhibit GVHD in lethally-irradiated mice receiving allogeneic hematopoietic cell transplantation (allo-HCT). However, some studies suggest that IFN- may promote lethality in unirradiated and sublethally-irradiated recipients. We investigated the role of IFN- in the induction of GVHD in sublethally-irradiated B6D2F1 mice receiving allo-HCT from B6 donors. B6D2F1 mice receiving wild-type B6 splenocytes alone died rapidly, while those receiving wild-type B6 splenocytes plus marrow survived long-term. Mice in both groups showed rapid elimination of host hematopoietic cells, but minimal parenchymal tissue injury. However, mice receiving allo-HCT from IFN--deficient donors died rapidly regardless of whether donor marrow was given, and they exhibited severe parenchymal tissue injury, but prolonged survival of host hematopoietic cells. IFN- plays a similar role in another model involving delayed B6 donor leukocyte infusion (DLI) to established mixed allogeneic (B6BALB/c) chimeras. IFN- promotes DLI-mediated conversion from mixed to full donor chimerism while attenuating GVHD. Importantly, IFN- enhances graft-versus-leukemia effects in both models. Our data indicate that previously reported IFN--induced early mortality in allo-HCT recipients is due to augmentation of lymphohematopoietic graft-vs.-host reactions, and can be avoided by providing an adequate source of donor hematopoietic stem/progenitor cells. Furthermore, the magnitude of graft-versus-leukemia effects is correlated with the strength of lymphohematopoietic graft-vs.-host reactions, and IFN- reduces the potential of this alloreactivity to cause epithelial tissue GVHD. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. K. Jasperson, C. Bucher, A. Panoskaltsis-Mortari, A. L. Mellor, D. H. Munn, and B. R. Blazar Inducing the tryptophan catabolic pathway, indoleamine 2,3-dioxygenase (IDO), for suppression of graft-versus-host disease (GVHD) lethality Blood, December 3, 2009; 114(24): 5062 - 5070. [Abstract] [Full Text] [PDF]

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