Authors: A C Inge Boullart Erik H J G Aarntzen Pauline Verdijk Joannes F M Jacobs Danita H Schuurhuis Daniel BenitezRibas Gerty Schreibelt Mandy W M M van de Rakt Nicole M Scharenborg Annemiek de Boer Matthijs Kramer Carl G Figdor Cornelis J A Punt Gosse J Adema I Jolanda M de Vries
Publish Date: 2008/03/06
Volume: 57, Issue: 11, Pages: 1589-1597
Abstract
Dendritic cells DC are professional antigenpresenting cells of the immune system that play a key role in regulating T cellbased immunity In vivo the capacity of DC to activate T cells depends on their ability to migrate to the T cell areas of lymph nodes as well as on their maturation state Depending on their cytokinesecreting profile DC are able to skew the immune response in a specific direction In particular IL12p70 producing DC drive T cells towards a T helper 1 type response A serious disadvantage of current clinical grade ex vivo generated monocytederived DC is the poor IL12p70 production We have investigated the effects of Tolllike receptor TLRmediated maturation on ex vivo generated human monocytederived DC We demonstrate that in contrast to cytokinematured DC DC matured with polyIC TLR3 ligand and/or R848 TLR7/8 ligand are able to produce vast amounts of IL12p70 but exhibit a reduced migratory capacity The addition of prostaglandin E2 PGE2 improved the migratory capacity of TLRligand matured DC while maintaining their IL12p70 production upon T cell encounter We propose a novel clinical grade maturation protocol in which TLR ligands polyIC and R848 are combined with PGE2 to generate DC with both high migratory capacity and IL12p70 production upon T cell encounter
Keywords: