Native human blood dendritic cells as potent effectors in antibody-dependent cellular cytotoxicity

Functional studies on native human dendritic cells (DCs) are hampered by technical difficulties in preparing fresh DCs. Recently, with the help of the monoclonal antibody M-DC8, we succeeded in isolating a major subpopulation of human blood DCs by a one-step immunomagnetic separation procedure. These cells strongly express Fc gamma RIII (CD16) and Fc gamma RII (CD32) and are quite efficient in the antigen-specific activation of naive T cells. Because some Fc gamma receptor-bearing cell types are known as effector cells in antibody-dependent cellular cytotoxicity (ADCC), we investigated whether M-DC8(+) DCs are capable of effectuating ADCC. In this report we show that freshly prepared M-DC8(+) DCs efficiently mediate tumor-directed ADCC and that both types of Fc gamma receptors as well as tumor necrosis factor alpha essentially contribute to the cytotoxic activity. The results provide evidence that, in addition to their pivotal role in primary T-cell activation, a subset of blood DCs displays efficient cytotoxicity in ADCC.