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Blood, 1 March 2008, Vol. 111, No. 5, pp. 2929-2940. Prepublished online as a Blood First Edition Paper on January 4, 2008; DOI 10.1182/blood-2007-06-096602. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-06-096602v1 111/5/2929    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 Kim, T. D. Articles by van den Brink, M. R. M. Search for Related Content PubMed PubMed Citation Articles by Kim, T. D. Articles by van den Brink, M. R. M. Related Collections Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Organ-derived dendritic cells have differential effects on alloreactive T cells Theo D. Kim1, Theis H. Terwey1, Johannes L. Zakrzewski1, David Suh1, Adam A. Kochman1, Megan E. Chen1, Chris G. King1, Chiara Borsotti1, Jeremy Grubin1, Odette M. Smith1, Glenn Heller2, Chen Liu3, George F. Murphy4, Onder Alpdogan1, and Marcel R. M. van den Brink1 1 Department of Medicine and Immunology, and 2 Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY; 3 Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville; and 4 Department of Pathology, Brigham and Women's Hospital, Boston, MA Dendritic cells (DCs) are considered critical for the induction of graft-versus-host disease (GVHD) after bone marrow transplantation (BMT). In addition to their priming function, dendritic cells have been shown to induce organ-tropism through induction of specific homing molecules on T cells. Using adoptive transfer of CFSE-labeled cells, we first demonstrated that alloreactive T cells differentially up-regulate specific homing molecules in vivo. Host-type dendritic cells from the GVHD target organs liver and spleen or skin- and gut-draining lymph nodes effectively primed naive allogeneic T cells in vitro with the exception of liver-derived dendritic cells, which showed less stimulatory capacity. Gut-derived dendritic cells induced alloreactive donor T cells with a gut-homing phenotype that caused increased GVHD mortality and morbidity compared with T cells stimulated with dendritic cells from spleen, liver, and peripheral lymph nodes in an MHC-mismatched murine BMT model. However, in vivo analysis demonstrated that the in vitro imprinting of homing molecules on alloreactive T cells was only transient. In conclusion, organ-derived dendritic cells can efficiently induce specific homing molecules on alloreactive T cells. A gut-homing phenotype correlates with increased GVHD mortality and morbidity after murine BMT, underlining the importance of the gut in the pathophysiology of GVHD. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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