...tained data on the effect of pro-inflammatory stroma-derived cytokines on DC in vivo. Our investigation has shown that, in the absence of additional stimuli, such inflammatory signals are ineffectual in promoting DC activation and cannot substitute for engagement of innate receptors directly on DC.

...rent studies favored the usage of distinct and restricted sets of cell surface markers and functional parameters. We obtained coexpression data of 18 genes simultaneously in individual cells from CD8+ T cell subsets (associated to multiple markers to subdivide CD8+ T cells into 14 different cell t...

...totoxic T cells by dendritic cells co-electroporated with a dsRNA analogue and tumor antigen mRNA. The maturation state of dendritic cells (DCs) is an important determinant for the initiation and regulation of adaptive immune responses. In this study, we wanted to assess whether functional activat...

...ctional tumor antigen-specific CD8+ T lymphocytes. In addition, CD83 mRNA-electroporated DC are stronger T cell stimulators. However, CD83 overexpression on Melan-A/MART-1-specific tumor-infiltrating lymphocytes (TIL) circumvents the need for CD83 expression on DC. Co-culture of immature DC with TIL...

...tained data on the activation of immature monocyte-derived dendritic cells after transduction with high doses of lentiviral vectors. Dendritic cells (DCs) are an attractive tool for immunomodulation, targeting mature DCs (mDCs) for immunization or immature/semimature DCs (iDCs) for tolerization. T...

...t as weak TLR9 agonist and that DNA bases short of CpG-motifs enhance this agonist activity. In contrast phospho-thioate (PS) modified abasic 2’ deoxyribose homopolymers act as TLR9 (and TLR7) agonists, but CpG-motifs convert the antagonistic function into agonist-activity. Interestingly, T cell...

.../- DC to activate T cell responses, in vitro and in vivo. Our data suggest that targeting p50 NF-kB activity may represent a strategy to enhance selective DC functions, with potential application in anti-tumor vaccination strategies. Protocols of antitumor vaccination will be set to explore the the...

...t enhanced leukocyte recruitment at the site of injection. Thus, hypoxia uncouples the promotion of inflammatory and tissue repair from sentinel functions in DCs, which we suggest is a safeguard mechanism against immune reactivity to damaged tissues. During the next period we wish to characterize t...

...DC migration and leads to their activation in lymph nodes but not lymph. These changes are due to TNF-alpha (migration) and Type 1 interferons (activation), but are not accompanied by obvious oral adjuvant effects. In contrast Etx causes only minor changes in migration and activation but is a potent...

...ctivation of naïve and memory T cells in rats. We have shown that 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 are currently examining the phenotype of the activated cells and determining if Treg...

...intestinal denritic cells are not constitutively biased towards stimluating Th2 responses (Milling). We have shown that antigen given orally during intestinal inflammation stimulates a strong response rather than tolerance.(Sebti). We have clarified the roles of dendritic cells and regulatory T cell...

...ty of TLR ligands was greatly improved through simultaneous administration of the iNKT cell ligand alpha-galactosylceramide. DC isolated from animals treated simultaneously with TLR and iNKT cell ligands were potent stimulators of naive T cells in vitro compared with DC from animals treated with the...

...e have obtained data from an analysis of antigen loading of DCs via targeting DC-SIGN, which resulted in enhanced class II-mediated presentation. Constructs for fusion proteins of the DC specific receptor DC-SIGN fused to GFP have been generated.

Our lab obtained data on maturation of DC by TLR agonists.

...the endosomal into the cytosolic compartment by combining antigen with cell penetrating peptides to further enhance cross-presentation. We made significant progress using biodegradable polymers to enhance cross-presentation of loaded antigens, and the best results were obtained by maturing DCs wit...

...ntation in DCs. In vivo, different subsets of DCs are considered with different competences to cross present antigens. The reasons why CD8+ DCs subset is the only one that efficiently carry out this phenomenon are not well understood. We have found that only CD8+ DCs display a NOX2 activity selecti...

...iated by regulatory CD4+ T lymphocytes. Adoptive transfer experiments of LACK-specific TCR transgenic T cells into newborn mice breastfed by LACK-exposed mothers demonstrated that LACK was readily processed and presented to T cells in the neonate. We then investigated whether the immune status of t...

...to attract other cell types. 2° We initiated a vast comparison between CD8 T cells responding to very different stimuli. Our preliminary results show that CD8 T cells responding either to virus or Listeria have very different properties, indicating that the inflammatory context defines CD8 T cell...

...moting T cell -dependent tumor rejection. In this Phase I trial using peptide-pulsed Dex, the observation of clinical regressions in the absence of T cell responses prompted the search for alternate effector mechanisms. Mouse studies unraveled the bioactivity of Dex onto NK cells, Dex promoting a ...

...intracellular pathogens to limit host immune pathology. IL-10 has been shown to exert its suppressive effect by directly acting on the antigen presenting cell (APC), therefore functioning to down-regulate macrophage antimicrobial activity or the induction of Th1 responses by dendritic cells (DC). ...