Monocytes and γδ T cells: close encounters in microbial infection

gamma delta T cells comprise an evolutionarily conserved yet poorly understood subset of T cells. Numerous features place these unconventional lymphocytes at the branching point between antigen-presenting cells and natural killer cells of the innate immune system and major-histocompatibility-complex-restricted alpha beta T cells of the adaptive immune system. We propose a role for human V gamma 9/V delta 2 T cells in the generation of monocyte-derived inflammatory dendritic cells during infection. Our model incorporates the peculiar innate-like specificity of V gamma 9/V delta 2 T cells for the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), co-recruitment of monocytes and V gamma 9/V delta 2 T cells to sites of infection, and their crosstalk, with profound consequences for the initiation of antigen-specific alpha beta T-cell responses. V gamma 9/V delta 2 T cells act thus as a cellular switch between innate and adaptive defence mechanisms.