Heterogeneity of long-term cultured activated killer cells induced by anti-T3 antibody

The present study has characterized the short term and long term cultured murine-activated killer (AK) cells that are induced by antibody directed against the epsilon-chain of T3 complex. The conventional lymphokine AK (LAK) cells were generated by culturing normal B6 spleen cells with purified human rIL-2. The alpha T3-induced AK cells (T3AK) were induced by culturing normal B6 spleen cells with alpha T3 and were then maintained in culture medium supplemented with human rIL-2 and/or alpha T3. After initial activation with alpha T3, lymphocyte proliferation and generation of cytotoxic effectors (T3AK) were noted, and these events were related to the endogenous production of IL-2 and IL-4. Addition of alpha IL-2 and/or alpha IL-4 suppressed both the proliferative response and the cytotoxic response induced by alpha T3. In comparing the T3AK cells with the conventional LAK cells, there were many similarities as well as some distinct differences. Both cells displayed a similar cytotoxic spectrum against a variety of tumor targets. The T3AK cells usually gave much higher levels of cytotoxic activity against susceptible targets. However, the susceptibility of different tumor targets to conventional LAK cells and T3AK cells varied. The time course for the generation of lytic activity also differed between the conventional LAK and T3AK cells. One distinct difference was their ability to survive in vitro. The conventional LAK cells survived in culture for only 1 wk. The T3AK cells could survive for at least 4 to 5 wk with active growth. The serologic phenotype of the LAK precursors was asialo GM1 (AsGM1+) cells, but the T3AK precursors could be either AsGM1+ or AsGM1-, depending on the target cell. The LAK effectors were both Lyt-2+ and Lyt-2-, but the short-term T3AK effectors were exclusively Lyt-2+. The long term T3AK cells (cultured for more than 2 wk) were found to consist of Lyt-2+ and Lyt-2- cells, and these subsets of T3AK cells showed different target specificities. These findings demonstrate the heterogeneity of LAK and T3AK cells, and this heterogeneous property may contribute to their diversity in specificity against different tumor targets and thus may affect their effectiveness in the immunotherapy of cancer.