We have demonstrated that the NADPH oxidase NOX2 is recruited to DC early phagosomes mediating a sustained production of low levels of reactive oxygen species and causing a maintained alkalynization of the phagosomal lumen. DCs lacking NOX2 show increased antigen degradation due to an enhanced phagosome acidification. As a result, the efficiency of in vitro and in vivo antigen cross presentation is significantly reduced in NOX2-deficient DCs.

These cells were primed in vitro by engineered antigen-presenting cells and used to investigate the effect of environmental factors on development of high affinity cytotoxic T lymphocytes (CTL).

CD83 overexpression on Melan-A/MART-1-specific tumor-infiltrating lymphocytes (TIL) circumvents the need for CD83 expression on DC.

These DC are exposed to HIV-1 to examine if this can directly modulate their functions or interfere with their cross-talk.

These monocyte-derived DCs received combined stimulation with TLR ligands. They were used in our study on DC activation by pathogen-derived stimuli.

We investigated the interactions between human monocyte derived DCs (MDDC), generated in the presence of GM-CSF and IL-4 (IL-4 DC), and antigen-stimulated circulating gamma delta T lymphocytes, bearing the Vgamma2 TCR.

The question was addressed of whether bLf, whose immunomodulant properties are now recognized, could influence MDDC differentiation/activation.

We wanted to assess whether functional activation of human monocyte-derived DCs can be achieved by electroporation of an activation signal in the form of double-stranded (ds) RNA and whether simultaneous electroporation of the dsRNA with tumor antigen encoding mRNA can lead to the induction of a cytotoxic T-lymphocyte (CTL) response.

We have analyzed the uptake, conservation and cross-presentation of the model antigen OVA after Fc receptor-mediated uptake by DC. We found that MHC class I presentation is relatively short-lived in contrast to MHC class II. However, CD8 cross-priming capacity of OVA-loaded DC was functionally retained for many days, while peptide-pulsed DC had lost their priming capacity after 24 hours.

We have analyzed the uptake, conservation and cross-presentation of the model antigen OVA after Fc receptor-mediated uptake by DC. We found that MHC class I presentation is relatively short-lived in contrast to MHC class II. However, CD8 cross-priming capacity of OVA-loaded DC was functionally retained for many days, while peptide-pulsed DC had lost their priming capacity after 24 hours.

We have studied the immuno-physiology of rat and mouse intestinal dendritic cells. We have used a known adjuvant, E. coli heat-labile toxin (Etx) and a potential adjuvant R-848, a small TLR7/8 ligand.

Direct administration of ovalbumin (OVA) encoding lentiviral vectors caused in vivo transduction of cells that were found in draining lymph nodes (LNs) and induced potent anti-OVA cytotoxic T cells similar to those elicited by ex vivo transduced DC.

Stimulation of Mycobacterium tuberculosis (MTb)-antigen specific T cells ex-vivo in the presence of anti-IL-10 antibodies results in their increased proliferation and IFN- production.

To quantify presentation of the epitopes by DC, we used bulk T cells electroporated with TCR-encoding RNA in stimulation assays.

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.

The DC were matured with TLR ligand R848 and polyI:C. Using these DC, we obtained best results in our evaluation whether antigens could be rerouted from the endosomal into the cytosolic compartment by combining antigen with cell penetrating peptides to further enhance cross-presentation.

We have studied the immuno-physiology of rat and mouse intestinal dendritic cells. We have used a known adjuvant, E. coli heat-labile toxin (Etx) and a potential adjuvant R-848, a small TLR7/8 ligand.

We are defining the differential roles of intestinal lymph DC subsets in activation of naïve and memory T cells. Two of the three DC subsets are highly potent activators of naïve CD4+ T cells, and do not appear to be constitutively suppressed in any way.

We have electroporated these DC with melanoma antigen RNA for a cross-presentation study and showed that they express the proteins ex vivo and in vivo.

We observed that ICAM-1 expression by mature DCs is critical for long-lasting contacts with CD8+ T cells, but dispensable for short-lived antigen-specific interactions. Serial brief T cell-dendritic cell contacts induced early CD8+ T cell activation, proliferation and effector CTL differentiation in the first few days after immunization.