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Blood, 25 June 2009, Vol. 113, No. 26, pp. 6593-6602. Prepublished online as a Blood First Edition Paper on April 30, 2009; DOI 10.1182/blood-2009-01-201467. This Article Full Text Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2009-01-201467v1 113/26/6593    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 Google Scholar Articles by Krebs, P. Articles by Hoebe, K. PubMed PubMed Citation Articles by Krebs, P. Articles by Hoebe, K. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY NK cell–mediated killing of target cells triggers robust antigen-specific T cell–mediated and humoral responses Philippe Krebs1, Michael J. Barnes1, Kristin Lampe2, Karen Whitley1, Keith S. Bahjat3, Bruce Beutler1, Edith Janssen2, and Kasper Hoebe2 1 Department of Genetics, The Scripps Research Institute, La Jolla, CA; 2 Division of Molecular Immunology, Cincinnati Children's Hospital Research Foundation, University of Cincinnati College of Medicine, OH; and 3 Robert W. Franz Cancer Center, Earle A. Chiles Research Institute, Providence Portland Medical Center, OR Previous work showed that administration of antigen-expressing apoptotic cells in vivo results in antigen-specific CD8+ T-cell responses independent of Toll-like receptor signaling. We report here that natural killer (NK) cells can serve a function directly upstream of this pathway and initiate robust adaptive immune responses via killing of antigen-expressing target cells. This pathway is highly sensitive, in that administration of as few as 104 target cells induced detectable antigen-specific CD8+ T-cell responses. Importantly, NK cell–mediated cytotoxicity of target cells could also induce robust antigen-specific CD4+ T-cell responses, which were critical for subsequent CD8+ T-cell priming and IgG responses. Unlike adaptive immune responses induced by gamma-irradiated cells, the NK-cell pathway required myeloid differentiating factor 88 (MyD88) and Toll/interleukin-1 receptor domain–containing adapter-inducinginterferon-β (Trif) signaling. NK cells have previously been shown to detect and kill pathogen-infected host cells, as well as neoplastic cells and tissue allografts. The present data provide further evidence that they also discharge a strong tie with their relatives in the adaptive immune system. We think that the recognition and killing of target cells by NK cells represents an important pathway for the generation of robust CD8+ T and humoral responses that may be exploited for vaccine development. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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