Potentiation of antigen-stimulated Vγ9Vδ2 T cell cytokine production by immature dendritic cells (DC) and recpirocal effect on DC maturation

V gamma 9V delta 2 T cells, a major gamma delta PBL subset in human adults, have been previously implicated in dendritic cell (DV) 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 V gamma 9V delta 2 T cells, the role played by DC subsets in activation of these lymphocytes has not been carefully studied so far. We show that MC, and to a lesser extent mature DC, potentiated Th1 and Th2 cytokine, but not cytolytic or proliferative responses, of established V gamma 9V delta 2 T cell clones and ex vivo memory V gamma 9V delta 2 PBL stimulated by synthetic agonists. The ability of iDC to potentiate V gamma 9V delta 2 production of inflammatory cytokines required for their own maturation suggested that V gamma 9V delta 2 T cells, despite their strong lytic activity, could promote efficient iDC licensing without killing at suboptimal Ag doses. Accordingly V gamma 9V delta 2 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 V gamma 9V delta 2 cells induced full differentiation into IL-12-producing cells of iDC infected by V gamma 9V delta 2-stimulating mycobacteria that were otherwise unable to induce complete DC maturation. In conclusion the ability of iDC to selectively potentiate cytokine response of memory V gamma 9V delta 2 T cells could underlie the adjuvant effect of these lymphocytes, and possibly other natural memory T cells, on conventional T cell responses.