Showing papers by "Elodie Segura published in 2009"

Membrane vesicles as conveyors of immune responses

Abstract: In multicellular organisms, communication between cells mainly involves the secretion of proteins that then bind to receptors on neighbouring cells But another mode of intercellular communication - the release of membrane vesicles - has recently become the subject of increasing interest Membrane vesicles are complex structures composed of a lipid bilayer that contains transmembrane proteins and encloses soluble hydrophilic components derived from the cytosol of the donor cell These vesicles have been shown to affect the physiology of neighbouring recipient cells in various ways, from inducing intracellular signalling following binding to receptors to conferring new properties after the acquisition of new receptors, enzymes or even genetic material from the vesicles This Review focuses on the role of membrane vesicles, in particular exosomes, in the communication between immune cells, and between tumour and immune cells

Different cross-presentation pathways in steady-state and inflammatory dendritic cells

Abstract: Presentation of exogenous antigens on MHC class I molecules, termed cross-presentation, is essential for the induction of CD8 T-cell responses and is carried out by specialized dendritic cell (DC) subsets. The mechanisms involved remain unclear. It has been proposed that antigens could be transported by endocytic receptors, such as the mannose receptor (MR) in the case of soluble ovalbumin, into early endosomes in which the cross-presentation machinery would be recruited. In these endosomal compartments, peptides would be trimmed by the aminopeptidase IRAP before loading onto MHC class I molecules. Here, we have investigated the contribution of this pathway to cross-presentation by steady-state CD8+ DC and inflammatory monocyte-derived DC (moDC) generated in vivo. We demonstrate that IRAP and MR are dispensable for cross-presentation by CD8+ DC and for cross-priming. Moreover, we could not find any evidence for diversion of endocytosed antigen into IRAP-containing endosomes in these cells. However, cross-presentation was impaired in moDC deficient in IRAP or MR, confirming the role of these two molecules in inflammatory DC. These results demonstrate that the mechanisms responsible for cross-priming by steady-state and inflammatory DC are different, which has important implications for vaccine design.

Characterization of an Immediate Splenic Precursor of CD8+ Dendritic Cells Capable of Inducing Antiviral T Cell Responses

Abstract: Mouse spleens contain three major dendritic cell (DC) populations: plasmacytoid DC, conventional CD8+CD24+ DC (CD8+ DC), and conventional CD8−CD24− DC (CD8− DC). We have previously shown that CD8+ DC are the major cross-presenting subtype in vivo and are the main inducers of antiviral cytotoxic T lymphocyte responses. Here we show that after depletion of CD8+ DC, the only DC capable of viral Ag presentation was a small subset that expresses CD24 but not CD8. This CD8−CD24+ DC population is greatly expanded in mice treated with the DC growth factor FMS-like tyrosine kinase 3 ligand. The CD8−CD24+ DC represent an immediate precursor of CD8+ DC, as demonstrated by their expression pattern of characteristic markers of CD8+ DC, their capacity to cross-present in vitro, and their conversion into CD8+ DC upon adoptive transfer into recipient mice. Accordingly, the lifespan of transferred CD8−CD24+ DC in vivo was greatly enhanced as compared with terminally differentiated CD8+ DC. Moreover, in a vaccination protocol, CD8−CD24+ DC induced stronger T cell responses and accelerated viral clearance of HSV-1 compared with CD8+ DC. Our results demonstrate that the ability to cross-present first appears in an immediate precursor population of CD8+ DC that does not yet express CD8. The enhanced capacity of CD8−CD24+ DC to induce immune responses upon adoptive transfer makes them an attractive novel tool for DC-based immunotherapies.

Cutting Edge: B220+CCR9− Dendritic Cells Are Not Plasmacytoid Dendritic Cells but Are Precursors of Conventional Dendritic Cells

Abstract: Mouse lymphoid organs contain two major subsets of dendritic cells (DC) that differ in their phenotype and functions: conventional DC (cDC) and plasmacytoid DC (pDC). Recently, it has been proposed that differential expression of CCR9 could distinguish functionally distinct pDC subsets. We show that B220(+)CCR9(-) DC do not express classical pDC markers and have a developmental origin different from that of pDC. Furthermore, B220(+)CCR9(-) DC do not secrete IFN-alpha in response to CpG and, unlike pDC, can efficiently present exogenous Ags. Our results demonstrate that B220(+)CCR9(-) DC do not represent a subset of pDC. After in vivo transfer, these cells down-regulate B220 expression and convert into the two major cDC subsets, showing that they are a developmental stage of cDC differentiation.