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Blood, 1 February 2007, Vol. 109, No. 3, pp. 1043-1050. Prepublished online as a Blood First Edition Paper on October 3, 2006; DOI 10.1182/blood-2005-12-024802. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2005-12-024802v1 109/3/1043    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 Lim, W. H. Articles by Coates, P. T. H. Search for Related Content PubMed PubMed Citation Articles by Lim, W. H. Articles by Coates, P. T. H. Related Collections Immunobiology Phagocytes Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Human plasmacytoid dendritic cells regulate immune responses to Epstein-Barr virus (EBV) infection and delay EBV-related mortality in humanized NOD-SCID mice Wai Hon Lim1,2, Svjetlana Kireta1, Graeme Randolph Russ1,2, and Patrick Toby Hewlett Coates1,2 From the1 Transplantation Immunology Laboratory and Department of Medicine, Queen Elizabeth Hospital, Adelaide, South Australia, Australia; 2 University of Adelaide, South Australia, Australia Epstein-Barr virus (EBV) is associated with posttransplant lymphoproliferative disease (PTLD), which is a leading cause of cancer death in recipients of transplants. We investigated the role of plasmacytoid dendritic cells (PDCs) in the development of EBV infection and the onset of lymphoproliferative disease (LPD) in humanized NOD-SCID mice and studied the effect of EBV on PDC function. NOD-SCID mice reconstituted with PDC-depleted peripheral blood mononuclear cells (PBMCs) from EBV IgG+ human donors had significantly enhanced mortality from disseminated EBV infection (median survival, 43 days) compared to PBMC-only mice (median survival, 72 days; log-rank P < .05). Mice reconstituted with PDC-enriched PBMCs challenged with EBV exhibited delayed mortality from EBV-LPD (median survival, 80 days) compared to PBMC-only mice challenged with EBV (median survival, 50 days; log-rank P < .05). EBV-stimulated pDCs produced interferon (IFN-) and promoted the activation of natural killer cells and IFN-–producing CD3+T cells. PDC activation of CD3+T cells in response to EBV stimulation was dependent on cell-to-cell contact, in part mediated by toll-like receptor 9 (TLR-9) signaling that was inhibited by chloroquine and TLR-9 inhibitory CpG. Thus, PDCs play an important role in anti-EBV cellular immune responses that may be targets for manipulation in novel strategies for the treatment of PTLD. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. Zucchini, G. Bessou, S. H. Robbins, L. Chasson, A. Raper, P. R. Crocker, and M. Dalod Individual plasmacytoid dendritic cells are major contributors to the production of multiple innate cytokines in an organ-specific manner during viral infection Int. Immunol., January 1, 2008; 20(1): 45 - 56. [Abstract] [Full Text] [PDF] S. Guggemoos, D. Hangel, S. Hamm, A. Heit, S. Bauer, and H. Adler TLR9 Contributes to Antiviral Immunity during Gammaherpesvirus Infection J. Immunol., January 1, 2008; 180(1): 438 - 443. [Abstract] [Full Text] [PDF] S. C. Barry and P. T. H. Coates Retroviral escape by Friendly infected DCs Blood, December 1, 2007; 110(12): 3819 - 3820. [Full Text] [PDF]

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