Essential role of high concentrations of interleukin-2 to maintain growth and functions of human interleukin-2-activated natural killer cells

We investigated the effects of interleukin-2 (IL-2) on growth and cytotoxic ity functions of human natural killer (NK) cells in culture. it is weil kno wn that a high dose of IL-2 is necessary to develop IL-2-activated NK (A-NK ) cells from human lymphocytes at an early stage in culture. After culture in the presence of 6,000 IU/ml of IL-2 for 10 days, A-NK cells were further incubated with or without 6,000 IU/ml of IL-2 for 48-96 h. Growth of A-NK cells was dependent on the presence of IL-2. Elimination of IL-2 resulted i n the down-regulation of IL-2 receptor alpha -chain expression and the up-r egulation of that of the beta -chain on A-NK cells. A-NK cells incubated wi th IL-2 had increased expression of Fas ligand and CD56, CD54 and CD11a mol ecules compared with the cells incubated without IL-2. A-NK cells incubated without IL-2 secreted both tumor necrosis factor (TNF)-alpha and interfero n (IFN)-gamma in significantly lower amounts than those secreted by the cel ls incubated with IL-2. After incubation with IL-2, A-NK cells showed that the cytolytic activity against NK-sensitive K-562 targets was significantly higher than that of A-NK cells after incubation without IL-2. While A-NK c ells after incubation with IL-2 also lysed NK-resistant HR targets, the cel ls incubated without IL-2 did not. in addition, A-NK cells after incubation with IL-2 induced DNA fragmentation in HR targets significantly more than in A-NK cells after incubation without IL-2. This study demonstrates that a high dose of IL-2 is necessary to maintain growth and some antitumor activ ities of A-NK cells.