Interleukin-2-activated human effector lymphocytes mediate cytotoxicity by inducing apoptosis in human leukaemia and solid tumour target cells.

The mode of cytotoxic action employed by cytolytic lymphocytes remains unclear, with the possibility of several mechanisms being utilized dependent upon the activation state of the effector cell. In this work, the induction of apoptosis in target cells by 'killer' lymphocytes at differing states of activation has been studied. Although the cytotoxicity of natural killer (NK) cells and recombinant human interleukin-2 (rhIL-2) or interferon-alpha (IFN-alpha)-activated effector cells, against NK-sensitive target cells, was high, their cytotoxic action appeared to be mediated via differing pathways. Effector cells activated short term (4 hr) with rhIL-2 and those mediating rhIL-2 lymphokine-activated killer (LAK) activity after long-term (4 day) activation were found to induce the formation of sodium dodecyl sulphate (SDS)-insoluble apoptotic bodies in NK-sensitive target cells, as well as increasing the level of activity of the apoptosis related enzyme tissue transglutaminase, thus suggesting the induction of the apoptotic pathway as a means of effecting target cell death. Non-activated and short-term (4 hr) IFN-alpha-activated effector cells did not appear to utilize this pathway in the target cell as their means of cytotoxicity. Effector cells showing LAK activity were also cytotoxic towards NK-insensitive cells, and this cytotoxicity again appeared to be mediated via the apoptotic pathway.