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Blood, 1 February 2006, Vol. 107, No. 3, pp. 1031-1038. Prepublished online as a Blood First Edition Paper on October 11, 2005; DOI 10.1182/blood-2005-04-1737. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-04-1737v1 107/3/1031    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 Kawamura, K. Articles by Uchiyama, T. Search for Related Content PubMed PubMed Citation Articles by Kawamura, K. Articles by Uchiyama, T. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Virus-stimulated plasmacytoid dendritic cells induce CD4+ cytotoxic regulatory T cells Kazuko Kawamura, Norimitsu Kadowaki, Toshio Kitawaki, and Takashi Uchiyama From the Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Immune responses to pathogens need to be maintained within appropriate levels to minimize tissue damage, whereas such controlled immunity may allow persistent infection of certain types of pathogens. Interleukin 10 (IL-10) plays an important role in such immune regulation. We previously showed that HSV-stimulated human plasmacytoid dendritic cells (pDCs) induced naive CD4+ T cells to differentiate into interferon (IFN-)/IL-10–producing T cells. Here we show that HSV-stimulated pDCs induce allogeneic naive CD4+ T cells to differentiate into cytotoxic regulatory T cells that poorly proliferate on restimulation and inhibit proliferation of coexisting naive CD4+ T cells. IL-3–stimulated pDCs or myeloid DCs did not induce such regulatory T cells. Both IFN- and IL-10 were responsible for the induction of anergic and regulatory properties. High percentages of CD4+ T cells cocultured with HSV-stimulated pDCs, and to a lesser extent those cocultured with IL-3–stimulated pDCs, expressed granzyme B and perforin in an IL-10–dependent manner. CD4+ T cells cocultured with HSV-stimulated pDCs accordingly exhibited cytotoxic activity. The finding that virus-stimulated pDCs are capable of inducing CD4+ cytotoxic regulatory T cells suggests that this DC subset may play an important role in suppressing excessive inflammatory responses and also in inducing persistent viral infection. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Iparraguirre, J. W. Tobias, S. E. Hensley, K. S. Masek, L. L. Cavanagh, M. Rendl, C. A. Hunter, H. C. Ertl, Ulrich. H. von Andrian, and W. Weninger Two distinct activation states of plasmacytoid dendritic cells induced by influenza virus and CpG 1826 oligonucleotide J. Leukoc. Biol., March 1, 2008; 83(3): 610 - 620. [Abstract] [Full Text] [PDF] V. Veckman and I. Julkunen Streptococcus pyogenes activates human plasmacytoid and myeloid dendritic cells J. Leukoc. Biol., February 1, 2008; 83(2): 296 - 304. [Abstract] [Full Text] [PDF] T. Tanijiri, T. Shimizu, K. Uehira, T. Yokoi, H. Amuro, H. Sugimoto, Y. Torii, K. Tajima, T. Ito, R. Amakawa, et al. Hodgkin's Reed-Sternberg cell line (KM-H2) promotes a bidirectional differentiation of CD4+CD25+Foxp3+ T cells and CD4+ cytotoxic T lymphocytes from CD4+ naive T cells J. Leukoc. Biol., September 1, 2007; 82(3): 576 - 584. [Abstract] [Full Text] [PDF] E. O. Kvale, Y. Floisand, F. Lund-Johansen, H. Rollag, L. Farkas, S. Ghanekar, P. Brandtzaeg, F. L. Jahnsen, and J. Olweus Plasmacytoid DCs regulate recall responses by rapid induction of IL-10 in memory T cells Blood, April 15, 2007; 109(8): 3369 - 3376. [Abstract] [Full Text] [PDF] L. Gabriele, A. Fragale, P. Borghi, P. Sestili, E. Stellacci, M. Venditti, G. Schiavoni, M. Sanchez, F. Belardelli, and A. Battistini IRF-1 deficiency skews the differentiation of dendritic cells toward plasmacytoid and tolerogenic features J. Leukoc. Biol., December 1, 2006; 80(6): 1500 - 1511. [Abstract] [Full Text] [PDF] A. Hosmalin and P. Lebon Type I interferon production in HIV-infected patients J. Leukoc. Biol., November 1, 2006; 80(5): 984 - 993. [Abstract] [Full Text] [PDF] H. Donaghy, J. Wilkinson, and A. L. Cunningham HIV interactions with dendritic cells: has our focus been too narrow? J. Leukoc. Biol., November 1, 2006; 80(5): 1001 - 1012. [Abstract] [Full Text] [PDF] A. Casrouge, S.-Y. Zhang, C. Eidenschenk, E. Jouanguy, A. Puel, K. Yang, A. Alcais, C. Picard, N. Mahfoufi, N. Nicolas, et al. Herpes Simplex Virus Encephalitis in Human UNC-93B Deficiency Science, October 13, 2006; 314(5797): 308 - 312. [Abstract] [Full Text] [PDF]

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