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Blood, 1 December 2006, Vol. 108, No. 12, pp. 3792-3800. Prepublished online as a Blood First Edition Paper on August 17, 2006; DOI 10.1182/blood-2006-02-004978. This Article Full Text Full Text (PDF) Supplemental Table and Figure All Versions of this Article: blood-2006-02-004978v1 108/12/3792    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 Schmidlin, H. Articles by Blom, B. Search for Related Content PubMed PubMed Citation Articles by Schmidlin, H. Articles by Blom, B. Related Collections Chemokines, Cytokines, and Interleukins Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Stimulated plasmacytoid dendritic cells impair human T-cell development Heike Schmidlin, Wendy Dontje, Fedde Groot, Suzanne J. Ligthart, Arnaud D. Colantonio, Monique E. Oud, Esther J. Schilder-Tol, Marcel Spaargaren, Hergen Spits, Christel H. Uittenbogaart, and Bianca Blom From the Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, The Netherlands; Department of Human Retrovirology, Academic Medical Center, University of Amsterdam, The Netherlands; Department of Pathology, Academic Medical Center, University of Amsterdam, The Netherlands; Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California–Los Angeles (UCLA); and Department of Pediatrics, David Geffen School of Medicine, UCLA. Thymic plasmacytoid dendritic cells (pDCs) are located predominantly in the medulla and at the corticomedullary junction, the entry site of bone marrow–derived multipotential precursor cells into the thymus, allowing for interactions between thymic pDCs and precursor cells. We demonstrate that in vitro–generated pDCs stimulated with CpG or virus impaired the development of human autologous CD34+CD1a– thymic progenitor cells into the T-cell lineage. Rescue by addition of neutralizing type I interferon (IFN) antibodies strongly implies that endogenously produced IFN-/ is responsible for this inhibitory effect. Consistent with this notion, we show that exogenously added IFN- had a similar impact on IL-7– and Notch ligand–induced development of thymic CD34+CD1a– progenitor cells into T cells, because induction of CD1a, CD4, CD8, and TCR/CD3 surface expression and rearrangements of TCR V-DJ gene segments were severely impaired. In addition, IL-7–induced proliferation but not survival of the developing thymic progenitor cells was strongly inhibited by IFN-. It is evident from our data that IFN- inhibits the IL-7R signal transduction pathway, although this could not be attributed to interference with either IL-7R proximal (STAT5, Akt/PKB, Erk1/2) or distal (p27kip1, pRb) events. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M.-L. Baron, D. Gauchat, R. La Motte-Mohs, N. Kettaf, A. Abdallah, T. Michiels, J.-C. Zuniga-Pflucker, and R.-P. Sekaly TLR Ligand-Induced Type I IFNs Affect Thymopoiesis J. Immunol., June 1, 2008; 180(11): 7134 - 7146. [Abstract] [Full Text] [PDF]

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