Plasticity of dendritic cell function in response to prostaglandin E2 (PGE2) and interferon-gamma (IFN-gamma).

Current evidence suggests that maturing dendritic cells (DCs) acquire a migratory phenotype to induce T cell responses in lymph nodes or a proinflammatory phenotype to condition the microenvironment at peripheral sites. We show that the interplay of PGE(2) and IFN-gamma generates a more complex pattern of mixed DC phenotypes in response to TLR stimulation. DCs activated by the TLR ligand R-848 in the presence of IFN-gamma and PGE(2) produced high levels of IL-12p70 and IL-23, started migration toward CCL19 within only 10 h, and still continued to secrete IL-12p70 without further restimulation following the migration step.

Efficient chemokine-dependent migration and primary and secondary IL-12 secretion by human dendritic cells stimulated through Toll-like receptors.

Recent findings have demonstrated the properties of cell migration and cytokine secretion to be mutually exclusive and linked them to different functional subpopulations of dendritic cells (DCs). We studied human monocyte-derived DCs after stimulation with peptidoglycan (PGN), poly(I:C), lipopolysaccharide (LPS), and R848 (resiquimod) and found the resulting mature DCs to express CCR7, to migrate toward CCL19 and to be efficient primary interleukin (IL)-12 producers. Importantly, the potential for secondary production of large amounts of IL-12p70 in response to CD40 ligation was also preserved after stimulation by all Toll-like receptor (TLR) ligands.

Functional characterization of monocyte-derived dendritic cells generated under serumfree culture conditions.

The culture of human monocyte-derived dendritic cells (DCs) is typically performed in media containing human or fetal calf serum, supplements with the potential to influence the cells phenotype and their functional properties. Published clinical trails based on serumfree cultured DCs reported the use of the commercially available medium AIMV. In this study, we directly compared DCs generated in AIMV medium ("AIMV/sf-DCs") with DCs generated in RPMI supplemented with 2% human serum ("RPMI/HS-DCs") in functional assays of potential relevance for vaccine application.

HIV-1 Nef mimics an integrin receptor signal that recruits the polycomb group protein Eed to the plasma membrane.

The Nef protein of human and simian immunodeficiency virus (HIV/SIV) is believed to interfere with T cell activation signals by forming a signaling complex at the plasma membrane. Composition and function of the complex are not fully understood. Here we report that Nef recruits the Polycomb Group (PcG) protein Eed, so far known as a nuclear factor and repressor of transcription, to the membrane of cells.