SEARCH:   Advanced

Blood, 4 June 2009, Vol. 113, No. 23, pp. 5999-6010. Prepublished online as a Blood First Edition Paper on April 15, 2009; DOI 10.1182/blood-2008-10-183335. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-10-183335v1 113/23/5999    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 Kuns, R. D. Articles by Hill, G. R. Search for Related Content PubMed PubMed Citation Articles by Kuns, R. D. Articles by Hill, G. R. Related Collections Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Invariant natural killer T cell–natural killer cell interactions dictate transplantation outcome after -galactosylceramide administration Rachel D. Kuns1, Edward S. Morris1, Kelli P. A. MacDonald1, Kate A. Markey1, Helen M. Morris1, Neil C. Raffelt1, Tatjana Banovic1, Alistair L. J. Don1, Vanessa Rowe1, Angela C. Burman1, Andrew D. Clouston2, Camile Farah3, Gurdyal S. Besra4, Petr A. Illarionov4, Mark J. Smyth5, Steven A. Porcelli6, and Geoffrey R. Hill1 1 Queensland Institute of Medical Research, Brisbane, Australia; 2 Envoi Pathology, Brisbane, Australia; 3 Faculty of Oral Biology and Pathology, University of Queensland Centre for Clinical Research (UQCCR), University of Queensland, Brisbane, Australia; 4 School of Biosciences, University of Birmingham, Birmingham, United Kingdom; 5 Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Australia; and 6 Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY Invariant natural killer T cells (iNKT cells) have pivotal roles in graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effects. iNKT cells are activated through their T-cell receptors by glycolipid moieties (typically the -galactosylceramide [-GalCer] derivative KRN7000) presented within CD1d. We investigated the ability of modified -GalCer molecules to differentially modulate alloreactivity and GVL. KRN7000 and the N-acyl variant, C20:2, were administered in multiple well-established murine models of allogeneic stem cell transplantation. The highly potent and specific activation of all type I NKT cells with C20:2 failed to exacerbate and in most settings inhibited GVHD late after transplantation, whereas effects on GVL were variable. In contrast, the administration of KRN7000 induced hyperacute GVHD and early mortality in all models tested. Administration of KRN7000, but not C20:2, was found to result in downstream interleukin (IL)-12 and dendritic cell (DC)–dependent natural killer (NK)– and conventional T-cell activation. Specific depletion of host DCs, IL-12, or donor NK cells prevented this pathogenic response and the induction of hyperacute GVHD. These data demonstrate the ability of profound iNKT activation to modulate both the innate and adaptive immune response via the DC–NK-cell interaction and raise concern for the use of -GalCer therapeutically to modulate GVHD and GVL effects. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

	Copyright © 2009 by American Society of Hematology         Online ISSN: 1528-0020