CD56+ human blood dendritic cells effectively promote TH1-type γδ T-cell responses

CD56(+) human dendritic cells (DCs) have recently been shown to differentiate from monocytes in response to GM-CSF and type 1 interferon in vitro. We show here that CD56(+) cells freshly isolated from human peripheral blood contain a substantial subset of CD14(+)CD86(+)HLA-DR+ cells, which have the appearance of intermediate-sized lymphocytes but spontaneously differentiate into enlarged DC-like cells with substantially increased HLA-DR and CD86 expression or into fully mature CD83(+) DCs in response to appropriate cytokines. Stimulation of CD56(+) cells containing both DCs and abundant gamma delta T cells with zoledronate and interleukin-2 (IL-2) resulted in the rapid expansion of gamma delta T cells as well as in IFN-gamma, TNF-alpha, and IL-1 beta but not in IL-4, IL-10, or IL-17 production. IFN-gamma, TNF-alpha, and IL-1 beta production were almost completely abolished by depleting CD14(+) cells from the CD56(+) subset before stimulation. Likewise, depletion of CD14(+) cells dramatically impaired gamma delta T-cell expansion. IFN-gamma production could also be blocked by neutralizing the effects of endogenous IL-1 beta and TNF-alpha. Conversely, addition of recombinant IL-1 beta, TNF-alpha, or both further enhanced IFN-gamma production and strongly up-regulated IL-6 production. Our data indicate that CD56(+) DCs from human blood are capable of stimulating CD56(+) gamma delta T cells, which may be harnessed for immunotherapy. (Blood. 2009;114:4422-4431)