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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.


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IMMUNOBIOLOGY

NK-dependent DC maturation is mediated by TNF{alpha} and IFN{gamma} 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 {alpha} (TNF{alpha}) (and interferon {gamma} [IFN{gamma}]) 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{alpha} 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.


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