Submitted August 20, 2007
Accepted January 8, 2008
Cognate CD4+ T cell-dendritic cell interactions induce migration of immature dendritic cell through dissolution of their podosomes
Cinzia Nobile, Marianne Lind, Francesc Miro, Karine Chemin, Marie Tourret, Giovanni Occhipinti, Stephanie Dogniaux, Sebastian Amigorena, and Claire Hivroz*
Institut Curie, Centre de Recherche, Paris, France
INSERM, Unite 653, Immunite et Cancer, Paris, France
Seismological Laboratory, Caltech, Pasadena, CA, United States
* Corresponding author; email: claire.hivroz{at}curie.fr.
Dendritic cells (DC) 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 DC induce DC maturation. We show here that CC chemokines produced during antigen-specific T-DC interactions also induce strong morphological modifications and migration of immature DC. 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 DC, i.e. podosomes. We thus propose a model in which chemokines secreted during Ag-specific contact between T cells and DC induce disassembly of interacting and neighboring immature DC podosomes, leading to recruitment of more immature DC towards sites of antigenic stimulation and to amplification of T cell responses.
