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Blood, 15 December 2007, Vol. 110, No. 13, pp. 4278-4284. Prepublished online as a Blood First Edition Paper on August 2, 2007; DOI 10.1182/blood-2007-06-096875. This Article Full Text Full Text (PDF) Supplemental Figure and Videos All Versions of this Article: blood-2007-06-096875v1 110/13/4278    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 Bouma, G. Articles by Thrasher, A. J. Search for Related Content PubMed PubMed Citation Articles by Bouma, G. Articles by Thrasher, A. J. Related Collections Immunobiology Cytoskeleton Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Impaired T-cell priming in vivo resulting from dysfunction of WASp-deficient dendritic cells Gerben Bouma1, Siobhan Burns1,2, and Adrian J. Thrasher1,2 1 Institute of Child Health, University College London (UCL), Molecular Immunology Unit, London; and 2 Great Ormond Street Hospital for Children National Health Service Trust, London, United Kingdom The Wiskott-Aldrich syndrome (WAS) is characterized by defective cytoskeletal dynamics affecting multiple immune cell lineages, and leading to immunodeficiency and autoimmunity. The contribution of dendritic cell (DC) dysfunction to the immune dysregulation has not been defined, although both immature and mature WAS knockout (KO) DCs exhibit significant abnormalities of chemotaxis and migration. To exclude environmental confounders as a result of WAS protein (WASp) deficiency, we studied migration and priming activity of WAS KO DCs in vivo after adoptive transfer into wild-type recipient mice. Homing to draining lymph nodes was reduced and WAS KO DCs failed to localize efficiently in T-cell areas. Priming of both CD4+ and CD8+ T lymphocytes by WAS KO DCs preloaded with antigen was significantly decreased. At low doses of antigen, activation of preprimed wild-type CD4+ T lymphocytes by WAS KO DCs in vitro was also abrogated, suggesting that there is a threshold-dependent impairment even if successful DC–T cell colocalization is achieved. Our data indicate that intrinsic DC dysfunction due to WASp deficiency directly impairs the T-cell priming response in vivo, most likely as a result of inefficient migration, but also possibly influenced by suboptimal DC-mediated cognate interaction. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Pulecio, E. Tagliani, A. Scholer, F. Prete, L. Fetler, O. R. Burrone, and F. Benvenuti Expression of Wiskott-Aldrich Syndrome Protein in Dendritic Cells Regulates Synapse Formation and Activation of Naive CD8+ T Cells J. Immunol., July 15, 2008; 181(2): 1135 - 1142. [Abstract] [Full Text] [PDF]

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