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Original Article

¹ Department of Pathology, Section of Immunology, University of Verona, 37100 Verona, Italy
² Schering-Plough Research Institute, Laboratory for Immunological Research, 69571 Dardilly, France

Address correspondence to Franca Gerosa, Department of Pathology, Section of Immunology, University of Verona, Policlinico G.B. Rossi, 37100 Verona, Italy. Phone: 39-045-8074007; Fax: 39-045-8202459; E-mail: franca.gerosa{at}univr.it

We analyzed the interaction between human peripheral blood natural killer (NK) cells and monocyte-derived immature dendritic cells (DC). Fresh NK cells were activated, as indicated by the induced expression of the CD69 antigen, and their cytolytic activity was strongly augmented by contact with lipopolysaccharide (LPS)-treated mature DC, or with immature DC in the presence of the maturation stimuli LPS, Mycobacterium tuberculosis or interferon (IFN)-. Reciprocally, fresh NK cells cultured with immature DC in the presence of the maturation stimuli strongly enhanced DC maturation and interleukin (IL)-12 production. IL-2–activated NK cells directly induced maturation of DC and enhanced their ability to stimulate allogeneic naive CD4⁺ T cells. The effects of NK cells were cell contact dependent, although the secretion of IFN- and TNF also contributed to DC maturation. Within peripheral blood lymphocytes the reciprocal activating interaction with DC was restricted to NK cells, because the other lymphocyte subsets were neither induced to express CD69, nor induced to mature in contact with DC. These data demonstrated for the first time a bidirectional cross talk between NK cells and DC, in which NK cells activated by IL-2 or by mature DC induce DC maturation.

Key Words: dendritic cell maturation • cytotoxicity • natural killer cells • cytokines • human

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• Vitale, M., Chiesa, M. D., Carlomagno, S., Pende, D., Arico, M., Moretta, L., Moretta, A. (2005). NK-dependent DC maturation is mediated by TNF{alpha} and IFN{gamma} released upon engagement of the NKp30 triggering receptor. Blood 106: 566-571 [Abstract] [Full Text]  
• Semino, C., Angelini, G., Poggi, A., Rubartelli, A. (2005). NK/iDC interaction results in IL-18 secretion by DCs at the synaptic cleft followed by NK cell activation and release of the DC maturation factor HMGB1. Blood 106: 609-616 [Abstract] [Full Text]  
• Warren, H. S., Jones, A. L., Freeman, C., Bettadapura, J., Parish, C. R. (2005). Evidence That the Cellular Ligand for the Human NK Cell Activation Receptor NKp30 Is Not a Heparan Sulfate Glycosaminoglycan. J. Immunol. 175: 207-212 [Abstract] [Full Text]  
• Zanoni, I., Foti, M., Ricciardi-Castagnoli, P., Granucci, F. (2005). TLR-Dependent Activation Stimuli Associated with Th1 Responses Confer NK Cell Stimulatory Capacity to Mouse Dendritic Cells. J. Immunol. 175: 286-292 [Abstract] [Full Text]  
• Adam, C., King, S., Allgeier, T., Braumuller, H., Luking, C., Mysliwietz, J., Kriegeskorte, A., Busch, D. H., Rocken, M., Mocikat, R. (2005). DC-NK cell cross talk as a novel CD4+ T-cell-independent pathway for antitumor CTL induction. Blood 106: 338-344 [Abstract] [Full Text]  
• Jiang, X.-X., Zhang, Y., Liu, B., Zhang, S.-X., Wu, Y., Yu, X.-D., Mao, N. (2005). Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells. Blood 105: 4120-4126 [Abstract] [Full Text]  
• Trivedi, P. P., Roberts, P. C., Wolf, N. A., Swanborg, R. H. (2005). NK Cells Inhibit T Cell Proliferation via p21-Mediated Cell Cycle Arrest. J. Immunol. 174: 4590-4597 [Abstract] [Full Text]  
• Steigerwald, M., Moll, H. (2005). Leishmania major Modulates Chemokine and Chemokine Receptor Expression by Dendritic Cells and Affects Their Migratory Capacity. Infect. Immun. 73: 2564-2567 [Abstract] [Full Text]  
• Marcenaro, E., Chiesa, M. D., Bellora, F., Parolini, S., Millo, R., Moretta, L., Moretta, A. (2005). IL-12 or IL-4 Prime Human NK Cells to Mediate Functionally Divergent Interactions with Dendritic Cells or Tumors. J. Immunol. 174: 3992-3998 [Abstract] [Full Text]  
• Gao, N., Dang, T., Dunnick, W. A., Collins, J. T., Blazar, B. R., Yuan, D. (2005). Receptors and Counterreceptors Involved in NK-B Cell Interactions. J. Immunol. 174: 4113-4119 [Abstract] [Full Text]  
• Schmitz, M., Zhao, S., Deuse, Y., Schakel, K., Wehner, R., Wohner, H., Holig, K., Wienforth, F., Kiessling, A., Bornhauser, M., Temme, A., Rieger, M. A., Weigle, B., Bachmann, M., Rieber, E. P. (2005). Tumoricidal Potential of Native Blood Dendritic Cells: Direct Tumor Cell Killing and Activation of NK Cell-Mediated Cytotoxicity. J. Immunol. 174: 4127-4134 [Abstract] [Full Text]  
• Makarenkova, V., Chakrabarti, A. K., Liberatore, J. A., Popovic, P., Lu, G., Watkins, S., Vujanovic, N. L. (2005). Dendritic cells and natural killer cells interact via multiple TNF family molecules. J. Leukoc. Biol. 77: 408-413 [Abstract] [Full Text]  

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