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Blood, 12 March 2009, Vol. 113, No. 11, pp. 2451-2460. Prepublished online as a Blood First Edition Paper on November 24, 2008; DOI 10.1182/blood-2008-05-157123. This Article Full Text (PDF) All Versions of this Article: blood-2008-05-157123v1 113/11/2451    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 Krause, P. Articles by Legler, D. F. Search for Related Content PubMed PubMed Citation Articles by Krause, P. Articles by Legler, D. F. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 16, 2008 Accepted October 9, 2008 Prostaglandin E2 enhances T cell proliferation by inducing the co-stimulatory molecules OX40L, CD70 and 4-1BBL on dendritic cells Petra Krause, Markus Bruckner, Christina Uermosi, Eva Singer, Marcus Groettrup, and Daniel F. Legler* Biotechnology Institute Thurgau, at the University of Konstanz, Kreuzlingen, Switzerland Klinikum Konstanz, Konstanz, Germany Department of Biology, Division of Immunology, University of Konstanz, Konstanz, Germany Zukunftskolleg, University of Konstanz, Konstanz, Germany * Corresponding author; email: daniel.legler{at}bitg.ch. Dendritic cell-based immunotherapy of malignant diseases relies on two critical parameters: antigen transport from the periphery to draining lymph nodes and efficient priming of primary and secondary immune responses. Prostaglandin E2 (PGE2) signaling has been shown to be pivotal for DC migration towards lymph node-derived chemokines in vitro and in vivo. Here, we demonstrate that PGE2 induced the expression of the co-stimulatory molecules OX40L, CD70, and 4-1BBL on human DCs. Short triggering by PGE2 early during DC maturation was sufficient to induce the co-stimulatory molecules. The expression of the co-stimulatory molecules was independent of the maturation stimulus but strictly dependent on PGE2 on both monocyte-derived (Mo)DCs and peripheral blood myeloid (PB)DCs. PGE2-matured MoDCs showed enhanced co-stimulatory capacities resulting in augmented antigen-specific CD4+ and CD8+ T cell proliferation in primary and recall T cell responses. Blocking OX40:OX40L signaling impaired the enhanced T cell proliferation induced by PGE2-matured MoDCs. Moreover, MoDCs matured in the presence of PGE2 induced the expression of OX40, OX40L, and CD70 on T cells facilitating T cell-T cell interaction that warrant long lasting co-stimulation. This newly identified parameter will help to further optimize DC-based immunotherapy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: V. A. Blaho, M. W. Buczynski, C. R. Brown, and E. A. Dennis Lipidomic Analysis of Dynamic Eicosanoid Responses during the Induction and Resolution of Lyme Arthritis J. Biol. Chem., August 7, 2009; 284(32): 21599 - 21612. [Abstract] [Full Text] [PDF] M. Hashimoto-Okada, T. Kitawaki, N. Kadowaki, S. Iwata, C. Morimoto, T. Hori, and T. Uchiyama The CD70-CD27 interaction during the stimulation with dendritic cells promotes naive CD4+ T cells to develop into T cells producing a broad array of immunostimulatory cytokines in humans Int. Immunol., August 1, 2009; 21(8): 891 - 904. [Abstract] [Full Text] [PDF] S. L. Highfill, R. M. Kelly, M. J. O'Shaughnessy, Q. Zhou, L. Xia, A. Panoskaltsis-Mortari, P. A. Taylor, J. Tolar, and B. R. Blazar Multipotent adult progenitor cells can suppress graft-versus-host disease via prostaglandin E2 synthesis and only if localized to sites of allopriming Blood, July 16, 2009; 114(3): 693 - 701. [Abstract] [Full Text] [PDF] A. M. Keller, Y. Xiao, V. Peperzak, S. H. Naik, and J. Borst Costimulatory ligand CD70 allows induction of CD8+ T-cell immunity by immature dendritic cells in a vaccination setting Blood, May 21, 2009; 113(21): 5167 - 5175. [Abstract] [Full Text] [PDF]

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