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9V
2 T Cell Cytokine Production by Immature Dendritic Cells (DC) and Reciprocal Effect on DC Maturation1
* Institut National de la Santé et de la Recherche Médicale, Unité 601, Nantes, France; and
Institut National de la Santé et de la Recherche Médicale, Unité 567, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8104, Paris, France
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9V
2 T cells, a major PBL subset in human adults, have been previously implicated in dendritic cell (DC) licensing, owing to their high frequency in peripheral tissues and their ability to produce inflammatory cytokines upon recognition of a broad array of conserved Ags. Although these observations implied efficient recognition of Ag-expressing immature DC (iDC) by V9V2 T cells, the role played by DC subsets in activation of these lymphocytes has not been carefully studied so far. We show that iDC, and to a lesser extent mature DC, potentiated Th1 and Th2 cytokine, but not cytolytic or proliferative responses, of established V9V2 T cell clones and ex vivo memory V9V2 PBL stimulated by synthetic agonists. The ability of iDC to potentiate V9V2 production of inflammatory cytokines required for their own maturation suggested that V9V2 T cells, despite their strong lytic activity, could promote efficient iDC licensing without killing at suboptimal Ag doses. Accordingly V9V2 cells induced accelerated maturation of Ag-expressing iDC but not "bystander" DC, even within mixed cell populations comprising both Ag-expressing and nonexpressing iDC. Furthermore V9V2 cells induced full differentiation into IL-12-producing cells of iDC infected by V9V2-stimulating mycobacteria that were otherwise unable to induce complete DC maturation. In conclusion the ability of iDC to selectively potentiate cytokine response of memory V9V2 T cells could underlie the adjuvant effect of these lymphocytes, and possibly other natural memory T cells, on conventional T cell responses.
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