Potentiation of Antigen-Stimulated Vγ9Vδ2 T Cell Cytokine Production by Immature Dendritic Cells (DC) and Reciprocal Effect on DC Maturation

Vγ9Vδ2 T cells, a major γδ 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 Vγ9Vδ2 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 Vγ9Vδ2 T cell clones and ex vivo memory Vγ9Vδ2 PBL stimulated by synthetic agonists. The ability of iDC to potentiate Vγ9Vδ2 production of inflammatory cytokines required for their own maturation suggested that Vγ9Vδ2 T cells, despite their strong lytic activity, could promote efficient iDC licensing without killing at suboptimal Ag doses. Accordingly Vγ9Vδ2 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 Vγ9Vδ2 cells induced full differentiation into IL-12-producing cells of iDC infected by Vγ9Vδ2-stimulating mycobacteria that were otherwise unable to induce complete DC maturation. In conclusion the ability of iDC to selectively potentiate cytokine response of memory Vγ9Vδ2 T cells could underlie the adjuvant effect of these lymphocytes, and possibly other natural memory T cells, on conventional T cell responses.