Since LPS-activated DC are potent inducers of NK cell priming and lymph nodes appear to be a key place in which DC and NK cell interactions occur, we have investigated the in vivo capacity of resting and DC-primed NK cells to reach the draining lymph nodes.

We have efficiently transfected DC with RNA encoding a functional protein (E/L-selectin), which allows entry of DC into LN from HEV. These DC rolled in vitro on sialyl-LewisX-coated slides, and in vivo, mouse E/L-selectin-transfected DC homed to LN after i.v. application.

We used dendritic cells loaded with anti-DEC205-antigen constructs, consisting of a single-chain variable fragment (scFv) directed against DEC-205, genetically linked to different parts of the MAGE-A3 model antigen (i.e. the KKl and EVDPIGHLY peptides), in a study to compare antigen-loading strategies.

For a transcriptional profiling of dendritic cells, DC were stimulated with PolyI:C, pretreated or not with PP2, and microarray analysis was performed.

These multipeptide loaded cytokine matured moDC +/- CD40L activation were used for the DERMA-ER-DC 04 trial.

We are currently performing gene silencing experiments in human monocyte-derived DCs (MDDCs) with the dual aim of generating relevant knowledge on (i) the transcriptional regulation of DC differentiation, and (ii) the safe and rationale in vitro manipulation of gene expression in DCs.

We have determined mechanisms for DC-induced Th1 development and the molecular pathways for inducing Th1 cells producing IFN-gamma solely, or Th1 cells producing IFN-gamma and IL-10, which have important implications for regulation of the immune response to eradicate pathogens with minimum pathology.

We have investigated the in vivo capacity of resting (and of DC-primed) NK cells to reach the draining lymph nodes.

Using pharmacological inhibitors, or macrophages and DC from mice carrying a null mutation in MAP kinase signalling molecule(s), we have evidence for a role of certain MAP kinases in the regulation of IL-10 and IL-12, IFN-gamma production.

My laboratory continued to analyse the ability of invariant NKT (iNKT) cells to assist priming of antigen specific T and B cell responses. We have demonstrated that activation of human DC by Toll like receptor ligands (TLR-L) modulates the lipid biosynthetic pathway, resulting in enhanced recognition of CD1d-associated lipids by iNKT cells; we have clarified the mechanisms by which CD1d-restricted lymphocytes translate T cell receptor (TCR) recognition of lipids with similar group heads into distinct biological responses; and we demonstrated that pathogen-derive...

We decided to analyze the protein changes that occur at the cell surface of a maturing DC, induced by a prototypical maturation stimulus such as LPS. Results obtained from the LC-MS/MS analysis of the integral plasma membrane proteome of D1 cells stimulated for 24 hours with LPS have been compared to the results obtained from immature D1 cells.