TUMOR-CELL DEATH INDUCED THROUGH THE RECEPTOR FOR INTERLEUKIN-2

We performed experiments to analyze the possible apoptotic effect of r ecombinant IL-2 on neoplastic cells expressing the receptor for IL-2. YAC-1 or EL/4 tumor cells, incubated in vitro with IL-2 or with monocl onal antibodies against the alfa-chain of the IL-2 receptor, underwent to apoptosis as analyzed by reduction in nuclear size, derangement in chromatin structure and DNA fragmentation in oligonucleosomal subunit s. The apoptotic phenomenon was time- and dose-dependent. Inhibition o f mRNA synthesis D-act or addition of IL-4 counteracted the effect of both IL-2 and anti-IL-2/r antibodies. Both rIL-2 or anti-IL-2/r mAb de termined an augmentation of phosphorilation pattern as measured by wes tern immunoblotting, and a transient augmentation of Ca++ as evaluated by a spectrophotometrical assay. These data suggest that stimulation of IL-2 receptor may induce an active process of cell death on neoplas tic cells in vitro.