Regulation of acquired immunity by γδ T-cell/dendritic-cell interactions

In humans, innate immune recognition of mycobacteria, including Mycobacterium tuberculosis and Mycobacterium leprae, involves toll-like receptor-2 (TLR-2), expressed on immature dendritic cells (DCs), and the T-cell gamma delta receptor expressed by a subpopulation of T cells that utilize V delta 2 (V delta 2 T cells). To investigate modulatory relationships between these host-cell populations in a microbial context, in vitro experiments were performed with human DCs and V delta 2 T cells stimulated with model TLR-2 ligands and phosphoantigens, respectively. We observed that TLR-2-stimulated DCs enhanced interferon-gamma (IFN-gamma) production by V delta 2 T cells; conversely, activated V delta 2 T cells enhanced TLR-2-induced DC maturation via soluble factors including IFN-gamma, which co-stimulated interleukin-12 (IL-12) p70 secretion by DCs. Exposure of DCs to activated V delta 2 T cells was critical for Th1 T-cell priming when TLR-2 stimulation was limiting. These results suggest that V delta 2 T cells may play an adjuvant role in priming protective antimycobacterial immunity when TLR-2 stimulation is lacking, as may occur if the infectious inoculum is small, or if the pathogen is an intrinsically weak activator of DCs.