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Blood, 15 July 2005, Vol. 106, No. 2, pp. 566-571. Prepublished online as a Blood First Edition Paper on March 22, 2005; DOI 10.1182/blood-2004-10-4035. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-10-4035v1 106/2/566    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Vitale, M. Articles by Moretta, A. Search for Related Content PubMed PubMed Citation Articles by Vitale, M. Articles by Moretta, A. Related Collections Immunobiology Phagocytes Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY NK-dependent DC maturation is mediated by TNF and IFN released upon engagement of the NKp30 triggering receptor Massimo Vitale, Mariella Della Chiesa, Simona Carlomagno, Daniela Pende, Maurizio Aricò, Lorenzo Moretta, and Alessandro Moretta From the Istituto Scientifico per la Ricerca sul Cancro (IST), Genova, Italy; Dipartimento di Medicina Sperimentale (DIMES), Università di Genova, Genova, Italy; Onco Ematologia Pediatrica, Ospedale dei Bambini G. Di Cristina, Palermo, Italy; Istituto Giannina Gaslini, Genova-Quarto, Italy; and Centro di Eccellenza per la Ricerca Biomedica, Genova, Italy. Natural killer (NK) cells were recently shown to play a relevant role in the process of dendritic cell (DC) maturation. This function is exerted either by direct DC stimulation or through killing those DCs that did not properly acquire a mature phenotype. While killing of immature DCs is dependent on the function of the NKp30 triggering receptor, the mechanism by which NK cells induce DC maturation is still unclear. In this study, we show that also the NK-mediated induction of DC maturation is dependent on NKp30. Upon NK/DC interaction, resulting in NKp30 engagement, NK cells produced tumor necrosis factor (TNF) (and interferon [IFN]) that, in turn, promoted DC maturation. Masking of NKp30 with specific monoclonal antibodies (mAbs) strongly reduced maturation of DCs cocultured with NK cells. In addition, supernatant from NK cells stimulated via NKp30 induced DC maturation, and this effect was neutralized by anti-TNF antibodies (Abs). This NKp30 function is controlled by the HLA-specific inhibitory NK receptors. Accordingly, the ability to promote maturation was essentially confined to NK cells expressing the killer immunoglobulin-like receptor–negative (KIR–) NKG2Adull phenotype. Finally, the analysis of perforin-deficient NK cells allowed the dissection of the 2 NKp30-mediated NK-cell functions, since NKp30 could induce cytokine-dependent DC maturation in the absence of NK-mediated DC killing. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Iannello, O. Debbeche, S. Samarani, and A. Ahmad Antiviral NK cell responses in HIV infection: II. viral strategies for evasion and lessons for immunotherapy and vaccination J. Leukoc. Biol., July 1, 2008; 84(1): 27 - 49. [Abstract] [Full Text] [PDF] E. Marcenaro, B. Ferranti, M. Falco, L. Moretta, and A. Moretta Human NK cells directly recognize Mycobacterium bovis via TLR2 and acquire the ability to kill monocyte-derived DC Int. 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