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Blood, 1 June 2007, Vol. 109, No. 11, pp. 5049-5057. Prepublished online as a Blood First Edition Paper on February 27, 2007; DOI 10.1182/blood-2007-01-067249. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-01-067249v1 109/11/5049    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by MacDonald, K. P. A. Articles by Hill, G. R. Search for Related Content PubMed PubMed Citation Articles by MacDonald, K. P. A. Articles by Hill, G. R. Related Collections Immunobiology Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Effector and regulatory T-cell function is differentially regulated by RelB within antigen-presenting cells during GVHD Kelli P. A. MacDonald1, Rachel D. Kuns1, Vanessa Rowe1, Edward S. Morris1, Tatjana Banovic1, Helen Bofinger1, Brendan O'Sullivan2, Kate A. Markey1, Alistair L. Don1, Ranjeny Thomas2, and Geoffrey R. Hill1 1 Bone Marrow Transplantation Laboratory, Queensland Institute of Medical Research, Herston, QLD, Australia; 2 Centre for Immunology and Cancer Research, University of Queensland, Princess Alexandra Hospital, Woolloongabba, QLD, Australia Antigen-presenting cells (APCs) are critical for the initiation of graft-versus-host disease (GVHD), although the responsible APC subset and molecular mechanisms remain unclear. Because dendritic cells (DCs) are the most potent APCs and the NF-kB/Rel family member RelB is associated with DC maturation and potent APC function, we examined their role in GVHD. Within 4 hours of total body irradiation, RelB nuclear translocation was increased and restricted to CD11chi DCs within the host APC compartment. Furthermore, the transient depletion of CD11chi donor DCs that reconstitute in the second week after transplantation resulted in a transient decrease in GVHD severity. By using RelB–/– bone marrow chimeras as transplant recipients or RelB–/– donor bone marrow, we demonstrate that the induction and maintenance of GVHD is critically dependent on this transcription factor within both host and donor APCs. Critically, RelB within APCs was required for the expansion of donor helper T cell type 1 (Th1) effectors and subsequent alloreactivity, but not the peripheral expansion or function of donor FoxP3+ regulatory T cells. These data suggest that the targeted inhibition of nuclear RelB translocation within APCs represents an attractive therapeutic strategy to dissociate effector and regulatory T-cell function in settings of Th1-mediated tissue injury. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. A. Markey, K. P. A. MacDonald, and G. R. Hill Recipient plasmacytoid DCs are not required to prime allogeneic T-cell responses after BMT Blood, June 4, 2009; 113(23): 6038 - 6039. [Full Text] [PDF] K. A. Markey, T. Banovic, R. D. Kuns, S. D. Olver, A. L. J. Don, N. C. Raffelt, Y. A. Wilson, L. J. Raggatt, A. R. Pettit, J. S. Bromberg, et al. Conventional dendritic cells are the critical donor APC presenting alloantigen after experimental bone marrow transplantation Blood, May 28, 2009; 113(22): 5644 - 5649. [Abstract] [Full Text] [PDF]

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