Enhancement of the antibody-dependent cellular cytotoxicity of human peripheral blood lymphocytes with interleukin-2 and interferon alpha.

Antibody-dependent cellular cytotoxicity (ADCC) is regarded as an important mechanism by which monoclonal antibodies (mAb) can exert an antitumour effect in vivo. It may be possible, therefore, to enhance the therapeutic efficacy of mAb by cytokines that are able to enhance the ADCC of human CD3-, CD56+, CD16+ natural killer (NK) cells. We investigated in vitro the effects of recombinant interferon alpha (rIFN alpha) and recombinant interleukin 2 (rIL-2), alone or in combination, on the ADCC of human peripheral blood NK cells. Both cytokines enhanced the ADCC of the human effector cells. rIFN alpha induced a maximally increased ADCC after an exposure of human effector cells to 20 IU/ml for 15-30 min, while rIL-2 induced optimal ADCC after incubation of the cells for 2 days in 20-50 U/ml. We now show that activation of the NK cells with a combination of rIL-2 and rIFN alpha induced significantly higher levels of ADCC than either cytokine alone. The highest ADCC was induced if the cells were first exposed to rIL-2 before rIFN alpha was added to the culture. Culture of NK cells in medium or rIL-2 decreased the expression of Fc gamma RIII (CD16), indicating that intensity of CD16 expression and level of ADCC are not directly correlated, although blocking experiments with a mAb directed against CD16 showed that this Fc gamma R was essential for ADCC of the human effector cells.