...ogy with the events following T-cell receptor (TCR) engagement leading to IL-2 production, it is therefore plausible that the stimulation of TLRs on DCs may lead to activation of the Ca2+/calcineurin and NFAT pathway. Our contribution to the project has been the finding that the DC stimulation with ...

...ggested that the molecules selectively produced by DC in presence of Th1 stimuli and not in presence of Th2 stimuli were type I IFNs and that these cytokines were presumably required for NK cell activation. In fact, our preliminary results confirmed this hypothesis with all of the Th1 stimuli tested...

...g relevant knowledge and data on (i) the transcriptional regulation of DC differentiation, and (ii) the safe and rationale in vitro manipulation of gene expression in DCs. One of the two different approaches that have been set up in parallel is: Transient transfection of synthetic siRNA: to t...

...us observations that large, non-phagocytisable Dectin-1 ligands are much more potent agonists than smaller ones. This is the first example of a bona fide signalling pathway from a cell surface innate receptor other than a TLR. We will continue to study innate signalling pathways in dendritic cell...

...articular, attention has been focussed on the recruitment of distinct subsets of DC to skin. This work, which is being performed in collaboration with PowderMed, a former SME now owned by Pfizer, may lead to the development of more targeted strategies to induce distinct T cell responses using this t...

... tetrameric iNKT TCR as a staining reagent we demonstrate specific up-regulation of CD1d-bound ligands upon TLR-mediated APC maturation. The ability of innate stimuli to modulate the lipid profile of DC resulting in iNKT cell activation, underscores the role of iNKT cells in assisting priming of ant...

...luating the role of ICOShi regulatory T cells in the intestine in steady state conditions and (3) the role of intestinal flora in the development of these cells using axenic mice. In parallel, we are testing whether the population of natural regulatory T cells (CD25+) control immune responses by act...

Our laboratory has obtained data on the role of DC-derived cytokines in NK cell production of IFN-gamma.

...lity at inducing T cell activation. Indeed we established that the mDC/pDC cross-talk has a functional effect on T cell activation. In fact the mDC/pDC cooperation event is able to significantly increase the ability of these cells to drive the proliferation and IFN? production by alloreactive T cell...

...o-cultured pDCs. Likewise, CpG-stimulated pDCs activate co-cultured mDCs. The cross talk between these two populations of DC is very efficient since it can be observed at mDC/pDC ratio ranging from 1/10 to 10/1. Activation of the co-cultured population is restricted to up-regulation of co-stimulator...

Our lab has obtained data on maturation stimuli for GMP-grade DC.

...the receptors on DCs responsible for capture of exosomes secreted by mature DCs. We have shown that expression of LFA-1, but not of Mac-1, integrin, on DCs is required for capture of ICAM-1-bearing exosomes. Furthermore, the CD8+ subpopulation of DCs in lymph nodes expresses LFA-1 at higher levels t...

... than tumors secreting soluble OVA, because they induce activation of OVA-specific CD8+ T cells into killer cells. In addition, inducing in vivo secretion of the C1C2-coupled antigen by DNA vaccination induces prevention against subsequent tumor growth. These results show for the first time a functi...

...tudies demonstrated for the first time the existence of a bidirectional activating interaction between DCs and gamma delta T lymphocytes activated by aminobiphosphonates. These data suggest a potential adjuvant role of this early cross-talk in the therapeutic activity of aminobiphosphonate drug that...

...lant properties are now recognized, on MDDC differentiation/activation. We found that bLF interferes with the activation of MD-DC induced by different TLR agonists, but not by T cell mediated signals. Although bLF did not significantly influence monocyte differentiation in DCs, we found that it mar...

...st combination and could represent a novel regulatory mechanism evolved to maintain immunological balance (Del Cornò et al.). Future studies will focus on - characterizing the mechanism(s) by which cross-tolerance between TLRs induce different functional states of DCs that favour different T cell...

...ure of DCs or gamma-delta T lymphocytes to HIV-1 can directly modulate their functions or interfere with their cross-talk. Preliminary results indicated that, although virus exposure of gamma-delta T cells does not significantly affect their properties, HIV-exposed DCs exhibit a reduced capacity to...

...t CTL expansion, effector function and CTL memory. In contrast, CTL that have received suboptimal stimulation fail to undergo extensive expansion. Nevertheless these arrested CTL persist long term and acquire memory function in the absence of further cell division. Thus our data demonstrate that CTL...

...strated that DCs enters an “unfolded protein response-like state and controls the phosphorylation of a key translation initiation factor (eIF2-a). The quality of the translation is not only affected, but the overall capacity of DCs to respond to stress is also modified in order to increase their ...

...tudies to demonstrate that DC can be activated via the dectin-1/Syk pathway to become APC capable of priming CD8+ T cells. In addition, we have shown that the same DC can interact with Tregs and convert them into cells that co-express ROR?t and Foxp3 and produce IL-17. We have shown that this pathw...