T Cell-Dependent Maturation of Dendritic Cells in Response to Bacterial Superantigens

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Abstract
Dendritic cells (DC) express a set of germline-encoded transmembrane Toll-like receptors that recognize shared microbial products, such as Escherichia coli LPS, termed pathogen-associated molecular patterns. Analysis of the in vivo response to pathogen-associated molecular patterns has uncovered their ability to induce the migration and the maturation of DC, favoring thus the delivery of Ag and costimulatory signals to naive T cells in vivo. Bacterial superantigens constitute a particular class of pathogen-derived molecules known to induce a potent inflammatory response in vivo, secondary to the activation of a large repertoire of T cells. We demonstrate in this work that Staphylococcal superantigens induce migration and maturation of DC populations in vivo. However, in contrast to LPS, superantigens failed to induce DC maturation in RAG or MHC class II-deficient mice, suggesting that T cell activation was a prerequisite for DC maturation. This conclusion was further supported by the finding that T cell activation induced by 1) mitogenic anti-CD3 mAbs, 2) allo-MHC determinants, or 3) nominal Ag in a TCR-transgenic model induces DC maturation in vivo. These studies also revealed that DC that matured in response to T cell mitogens display, comparatively to LPS, a distinctive phenotype characterized by high expression of the MHC class II, CD40, and CD205 markers, but only moderate (CD86) to minimal (CD80) expression of CD28/CTLA4 ligands. This work demonstrates that activation of a sufficient number of naive T cells in vivo constitutes a novel form of immune danger, functionally linked to DC maturation.