Portal de Periódicos da CAPES

Maturation of monocyte-derived dendritic cells with Toll-like receptor 3 and 7/8 ligands combined with prostaglandin E2 results in high interleukin-12 production and cell migration

2008; Springer Science+Business Media; Volume: 57; Issue: 11 Linguagem: Inglês

10.1007/s00262-008-0489-2

1432-0851

A.C.I. Boullart, Erik H.J.G. Aarntzen, Pauline Verdijk, Joannes F.M. Jacobs, Danita H. Schuurhuis, Daniel Benítez‐Ribas, 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,

T-cell and B-cell Immunology

Dendritic cells (DC) are professional antigen-presenting cells of the immune system that play a key role in regulating T cell-based 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 cytokine-secreting profile, DC are able to skew the immune response in a specific direction. In particular, IL-12p70 producing DC drive T cells towards a T helper 1 type response. A serious disadvantage of current clinical grade ex vivo generated monocyte-derived DC is the poor IL-12p70 production. We have investigated the effects of Toll-like receptor (TLR)-mediated maturation on ex vivo generated human monocyte-derived DC. We demonstrate that in contrast to cytokine-matured DC, DC matured with poly(I:C) (TLR3 ligand) and/or R848 (TLR7/8 ligand) are able to produce vast amounts of IL-12p70, but exhibit a reduced migratory capacity. The addition of prostaglandin E2 (PGE2) improved the migratory capacity of TLR-ligand matured DC while maintaining their IL-12p70 production upon T cell encounter. We propose a novel clinical grade maturation protocol in which TLR ligands poly(I:C) and R848 are combined with PGE2 to generate DC with both high migratory capacity and IL-12p70 production upon T cell encounter.