Induction of human NK cell-mediated cytotoxicity by CD40 triggering on antigen presenting cells

Rossella Sartorius, Luciana D'Apice, Pasquale Barba, John Guardiola, Angela Santoni, Francesca Velotti, Piergiuseppe De Berardinis

Research output: Contribution to journalArticlepeer-review

Abstract

Engagement of CD40 on antigen presenting cells (APC) is central to the initiation of cell-mediated immune response. Here, we investigated the ability of CD40 ligation on APC to induce NK cell-mediated cytotoxicity in the human system and the mechanism(s) underlying this process. We showed that APC (consisting in adherent peripheral blood mononuclear cells) (PBMC), pre-stimulated with anti-CD40 monoclonal antibodies and co-cultured with autologous non-adherent PBMC for 5-9 days, induced CD3-/CD56+ NK cell-mediated cytotoxicity as well as CD3+/CD56+ T cell-mediated unrestricted cytotoxic activity. The generation of NK cell-mediated cytotoxicity was independent on cell-to-cell contact between CD40-triggered APC and NK cells. Moreover, we found that IL-12 did not play a role in NK cells induction by anti-CD40 priming, while IL-2 and IL-15 did play a role. Our results provide an insight into the mechanism by which NK cells are activated in peripheral blood and useful informations for therapeutic application of anti-CD40 antibodies.

Original languageEnglish
Pages (from-to)81-88
Number of pages8
JournalCellular Immunology
Volume221
Issue number2
DOIs
Publication statusPublished - Feb 2003

Keywords

  • APC
  • CD3
  • CD56
  • IL-15
  • IL-2
  • Magnetic microbeads
  • NK
  • PBMC
  • Tumor immunity
  • Vaccines

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

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