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Prepublished online as a Blood First Edition Paper on July 31, 2003; DOI 10.1182/blood-2003-04-1244. This Article Full Text (PDF) All Versions of this Article: 2003-04-1244v1 102/12/4099    most recent Alert me when this article is cited Alert me if a correction is posted 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 Fontana, S. Articles by Badolato, R. Search for Related Content PubMed PubMed Citation Articles by Fontana, S. Articles by Badolato, R. Social Bookmarking                   What's this? Submitted April 24, 2003 Accepted July 22, 2003 Functional defects of dendritic cells in CD40-deficient patients Stefania Fontana, Daniele Moratto, Surinder Mangal, Maria De Francesco, William Vermi, Simona Ferrari, Fabio Facchetti, Necil Kutukculer, Claudia Fiorini, Marzia Duse, Pranab K Das, Luigi D Notarangelo, Alessandro Plebani, and Raffaele Badolato* Istituto di Medicina Molecolare, University of Brescia, Brescia, Italy Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Istituto di Microbiologia, University of Brescia, Brescia, Italy Cattedra di Anatomia Patologica, University of Brescia, Brescia, Italy Department of Pediatrics, Ege University, The Medical School, Izmir, Turkey Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Istituto di Medicina Molecolare, University of Brescia, Brescia, Italy * Corresponding author; email: badolato{at}master.cci.unibs.it. We have recently identified two patients with a rare autosomal recessive form of Hyper IgM disease, known as HIGM3, due to mutations in the CD40 gene. These patients presented opportunistic infections as observed in X-linked HIGM, suggesting that the CD40-CD40 ligand interaction is important for promoting T-cell mediated immunity. In order to evaluate whether innate immunity signals may substitute CD154 for inducing maturation of dendritic cells (DCs), we analyzed monocyte-derived DCs in these patients. Monocyte-derived DCs of HIGM3 subjects, upon ex vivo stimulation with TNF- or LPS combined with IFN-, normally express all the markers of mature DCs, such as CD83 and DC-LAMP. However, cell surface levels of HLA-DR in mature DCs are reduced, as is costimulatory activity of these cells for allogeneic naive T cells. In addition, CD40-deficient DCs secrete lower amounts of IL-12, but larger quantities of IL-10, in comparison to control subjects. Finally, analysis of circulating plasmacytoid DCs demonstrates a normal percentage of this subset in CD40-deficient cells, but IFN- secretion in response to HSV-1 infection is severely reduced in patients. These observations suggest that the severe impairment of DCs maturation may contribute to the defect of T-cell mediated immunity that is observed in HIGM3 patients. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. F. Skibola, A. Nieters, P. M. Bracci, J. D. Curry, L. Agana, D. R. Skibola, A. Hubbard, N. Becker, M. T. Smith, and E. A. Holly A functional TNFRSF5 gene variant is associated with risk of lymphoma Blood, April 15, 2008; 111(8): 4348 - 4354. [Abstract] [Full Text] [PDF] E. Sitati, E. E. McCandless, R. S. Klein, and M. S. Diamond CD40-CD40 Ligand Interactions Promote Trafficking of CD8+ T Cells into the Brain and Protection against West Nile Virus Encephalitis J. 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