The natural killer cell-mediated killing of autologous dendritic cells is confined to a cell subset expressing CD94/NKG2A, but lacking inhibitory killer Ig-like receptors

Mariella Della Chiesa, Massimo Vitale, Simona Carlomagno, Guido Ferlazzo, Lorenzo Moretta, Alessandro Moretta

Research output: Contribution to journalArticle

Abstract

The cognate NK-DC interaction in inflamed tissues results in NK cell activation and acquisition of cytotoxicity against immature DC (iDC). This may represent a mechanism of DC selection required for the control of downstream adaptive immune responses. Here we show that killing of monocyte-derived iDC is confined to the NK cell subset that expresses CD94/NKG2A, but not killer Ig-like receptors (KIR). Consistent with these data, the expression of HLA-E (i.e. the cellular ligand of CD94/NKG2A) was down-regulated in iDC. On the other hand, HLA-B and HLA-C down-regulation in iDC was not sufficient to induce cytotoxicity in NK cells expressing KIR3DL1 or KIR2DL. Remarkably, CD94/NKG2A+KIR- NK cells were heterogeneous in their ability to kill iDC and an inverse correlation existed between their CD94/NKG2A surface density and the magnitude of their cytolytic activity. It is conceivable that the reduced CD94/NKG2A surface density enables these cells to efficiently sense the decrease of HLA-E surface expression in iDC. Finally, most NK cells that lysed iDC did not kill mature DC that express higher amounts of HLA class I molecules (including HLA-E) as compared with iDC. However, a small NK cell subset was capable of killing not only iDC but also mature DC.

Original languageEnglish
Pages (from-to)1657-1666
Number of pages10
JournalEuropean Journal of Immunology
Volume33
Issue number6
DOIs
Publication statusPublished - Jun 1 2003

Keywords

  • Cytotoxicity
  • Dendritic cell
  • HLA-E
  • NK cell

ASJC Scopus subject areas

  • Immunology

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