Induction of human NK cell-mediated cytotoxicity by CD40 triggering on antigen presenting cells.
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.
Institute of Protein Biochemistry, CNR, via G. Marconi 10, 80125, Naples, Italy.
Rossella
R
Sartorius
Luciana
L
D'Apice
Pasquale
P
Barba
John
J
Guardiola
Angela
A
Santoni
Francesca
F
Velotti
Piergiuseppe
P
De Berardinis
D000911:Antibodies, Monoclonal / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology*; D023201:CD40 Ligand / Q000276:immunology; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D023201:CD40 Ligand