Cognate CD4(+) T-cell-dendritic cell interactions induce migration of immature dendritic cells through dissolution of their podosomes

Dendritic cells (DCs) control T cell-based immunity. To do so they need to mature and migrate to sites of T-cell priming. We have previously shown that cognate interactions of human CD4(+) T cells with DCs induce DC maturation. We show here that CC chemokines produced during antigen-specific T-DC interactions also induce strong morphologic modifications and migration of immature DCs. These modifications are required for efficient T-cell activation. Moreover, we show that CC chemokines produced during antigen-specific DC-T-cell interactions induce the dissolution of structures involved in cell motility and present on immature DCs (ie, podosomes). We thus propose a model in which chemokines secreted during Ag- specific contact between T cells and DCs induce disassembly of interacting and neighboring immature DC podosomes, leading to recruitment of more immature DCs toward sites of antigenic stimulation and to amplification of T-cell responses.