Recognition of autologous dendritic cells by human NK cells

Ennio Carbone, Giuseppe Terrazzano, Giuseppina Ruggiero, Delia Zanzi, Alessandro Ottaiano, Ciro Manzo, Klas Kärre, Serafino Zappacosta

Research output: Contribution to journalArticle

Abstract

NK cells can recognize and kill tumor as well as certain normal cells. The outcome of the NK-target interaction is determined by a balance of positive and negative signals initiated by different target cell ligands. We have previously shown that human NK cells kill CD40-transfected tumor targets efficiently, but the physiological significance of this is unclear. We now demonstrate that human NK cells can kill dendritic cells (DC), known to express CD40 and other co-stimulatory molecules. The killing was observed with polyclonal NK cells cultured short term in IL-2 as well as with NK cell clones as effectors, and with allogeneic as well as autologous DC as targets. NK cell recognition could be inhibited, but only partially, by preincubation of target cells with monoclonal antibodies against CD40, suggesting that this molecule may be one of several ligands involved. Addition of TNF-α of the cultures stimulated the development of a more mature DC phenotype, while addition of IL-10 resulted in a less mature phenotype, with lower expression of CD40 and other co-stimulatory molecules. Nevertheless, such DC were more NK susceptible than the differentiated DC. This may be partly explained by a reduced MHC class I expression observed on such cells, since blocking of MHC class I molecules on differentiated DC or CD94 receptors of NK cells led to increased NK susceptibility. The results show that NK cells may interact with DC, and suggest that the outcome of such interactions depend on the cytokine milieu.

Original languageEnglish
Pages (from-to)4022-4029
Number of pages8
JournalEuropean Journal of Immunology
Volume29
Issue number12
DOIs
Publication statusPublished - 1999

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Keywords

  • CD40
  • Cytokine
  • Dendritic cell
  • NK

ASJC Scopus subject areas

  • Immunology

Cite this

Carbone, E., Terrazzano, G., Ruggiero, G., Zanzi, D., Ottaiano, A., Manzo, C., Kärre, K., & Zappacosta, S. (1999). Recognition of autologous dendritic cells by human NK cells. European Journal of Immunology, 29(12), 4022-4029. https://doi.org/10.1002/(SICI)1521-4141(199912)29:12<4022::AID-IMMU4022>3.0.CO;2-O