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Prepublished online as a Blood First Edition Paper on June 21, 2002; DOI 10.1182/blood-2001-12-0360. This Article Full Text (PDF) All Versions of this Article: 2001-12-0360v1 100/4/1362    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 Luft, T. Articles by Maraskovsky, E. Search for Related Content PubMed PubMed Citation Articles by Luft, T. Articles by Maraskovsky, E. Social Bookmarking                   What's this? Submitted December 31, 2001 Accepted May 29, 2002 Functionally distinct DC populations induced by physiologic stimuli: prostaglandin E2 (PGE2) regulates the migratory capacity of specific DC subsets Thomas Luft, Michael Jefford, Petra Leutjens, Tracey Toy, Hubertus Hochrein, Kelly-Anne Masterman, Charlie Maliszewski, Ken Shortman, Jonathan Cebon, and Eugene Maraskovsky* Medizinische Klinik und Poliklinik V, University of Heidelberg, Heidelberg, Germany The Melbourne Tumour Biology Branch, Ludwig Institute for Cancer Research, Austin and Repatriation Medical Centre, Heidelberg, VIC, Australia Institut fur Experimentelle Hamatologie und Transfusionsmedizin Uniklinik Bonn, Bonn, Germany The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia Immunex Corporation, Seattle, WA, USA * Corresponding author; email: eugene.maraskovsky{at}ludwig.edu.au. Migration of Ag-loaded dendritic cells (DC) from sites of infection into draining lymphoid tissues is fundamental to the priming of T cell immune responses. We evaluated monocyte-derived DC (MoDC) and blood DC (PBDC) to respond to (1) pro-inflammatory mediators, (2) CD40L and (3) intact bacteria. All classes of stimuli induced DC phenotypic maturation. However, for MoDC, only PGE2-containing stimuli induced migratory-type DC. Thus, immature MoDC that encountered pro-inflammatory cytokines or CD40L or intact bacteria in the presence of PGE2 acquired migratory capacity but secreted low levels of cytokines. Conversely, MoDC that encountered pathogens or CD40L alone become non-migratory, cytokine secreting cells (pro-inflammatory type). Interestingly, both migratory and pro-inflammatory type DC expressed equivalent levels of chemokine receptors suggesting that the role of PGE2 was to switch on migratory function. We demonstrate that PGE2 induces migration via the EP2/EP4 receptors and the cAMP pathway. Finally, migratory-type MoDC stimulated T cell proliferation and predominantly IL-2 secretion, whereas pro-inflammatory-type MoDC induced IFN- production. In contrast, CD1b/c+ PBDC rapidly acquired migratory capacity irrespective of the class of stimulus encountered and secreted low levels of cytokines. This suggests that not all mature stages of DC are destined to migrate to lymphoid organs and that the sequence in which stimuli are encountered significantly affects which functions are expressed. Thus, certain immature DC subsets recruited from the resting precursor pool may have multiple functional fates that play distinct roles during the induction and effector phases of the immune response. These findings have important implications for the clinical utility of DC in immunotherapy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? 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