NK cell-mediated lysis of autologous antigen-presenting cells is triggered by the engagement of the phosphatidylinositol 3-kinase upon ligation of the natural cytotoxicity receptors NKp30 and NKp46

Grazia Maria Spaggiari, Roberta Carosio, Daniela Pende, Stefania Marcenaro, Paola Rivera, Maria Raffaella Zocchi, Lorenzo Moretta, Alessandro Poggi

Research output: Contribution to journalArticle

Abstract

Interleukin-2 (IL-2)-activated polyclonal or clonal NK cells lysed autologous antigen presenting cells (APC) through the engagement of the natural cytotoxicity receptors (NCR) NKp30 and NKp46. NK cell-mediated cytolysis of APC correlated with the surface density of these NCR. Indeed, NK cell clones bearing low amounts of NKp30 and NKp46 did not lyse autologous APC, whereas NK cell clones with bright expression of these NCR efficiently killed autologous APC. Upon masking of NKp30 or NKp46 by specific monoclonal antibodies a strong reduction (by 50%) of APC lysis could be detected and the complete inhibition was achieved by the simultaneous masking of these NCR. Interestingly, NK cell-mediated APC lysis was impaired by the phosphatidylinositol 3-kinase (PI-3 K) inhibitors LY294002 or wortmannin. Similarly, these drugs strongly reduced NK cell activation triggered by NKp30 or NKp46 in a re-directed killing assay as well as the activation of Akt/PKB, substrate of PI-3 K, induced by the engagement of these receptors. Altogether, these findings strongly suggest that NCR are responsible for the killing of autologous APC through the activation of PI-3 K.

Original languageEnglish
Pages (from-to)1656-1665
Number of pages10
JournalEuropean Journal of Immunology
Volume31
Issue number6
DOIs
Publication statusPublished - 2001

Keywords

  • APC
  • Dendritic cell
  • Natural cytotoxicity receptor
  • NK cell
  • Pl-3 K

ASJC Scopus subject areas

  • Immunology

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