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Blood, 21 May 2009, Vol. 113, No. 21, pp. 5167-5175. Prepublished online as a Blood First Edition Paper on March 11, 2009; DOI 10.1182/blood-2008-03-148007. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-03-148007v1 113/21/5167    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Keller, A. M. Articles by Borst, J. Search for Related Content PubMed PubMed Citation Articles by Keller, A. M. Articles by Borst, J. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Costimulatory ligand CD70 allows induction of CD8+ T-cell immunity by immature dendritic cells in a vaccination setting Anna M. Keller1, Yanling Xiao1, Victor Peperzak1, Shalin H. Naik1, and Jannie Borst1 1 Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands The use of dendritic cells (DCs) as anticancer vaccines holds promise for therapy but requires optimization. We have explored the potential of costimulatory ligand CD70 to boost the capacity of DCs to evoke effective CD8+ T-cell immunity. We show that immature conventional DCs, when endowed with CD70 expression by transgenesis, are converted from a tolerogenic state into an immunogenic state. Adoptively transferred CD70-expressing immature DCs could prime CD8+ T cells, by CD27, to become tumor-eradicating cytolytic effectors and memory cells with a capacity for robust secondary expansion. The CD8+ T-cell response, including memory programming, was independent of CD4+ T-cell help, because the transferred immature DCs were loaded with major histocompatibility complex class I–restricted peptide only. Without CD70 expression, the DCs generated abortive clonal expansion, dysfunctional antitumor responses, and no CD8+ T-cell memory. CD70-expressing CD8+ DCs were the primary subset responsible for CD8+ T-cell priming and performed comparably to fully matured DCs. These data highlight the importance of CD27/CD70 interactions at the T-cell/DC interface and indicate that CD70 should be considered in the design of DC vaccination strategies. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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