Lymphokine-induced cytotoxicity: characterization of effectors, precursors, and regulatory ancillary cells

In the present study, we have characterized the effectors, precursors, and regulatory ancillary cells involved in the in vitro generation of lymphokine-induced cytotoxicity. It was first shown that at least two lymphokines are needed for the generation of lymphokine-induced cytotoxicity. They are interleukin 2 and a novel lymphokine, the cytotoxic cell differentiation factor (CCDF). CCDF was produced primarily by the macrophages. The effectors of the lymphokine-induced cytotoxic cells thus generated selectively killed tumor targets of different etiological origins. The serological phenotype of lymphokine-induced cytotoxic cell effectors were found to be Thy 1+, Lyt 2-, and AGM1-; therefore, they were neither classic natural killer (NK) cells nor cytotoxic T-lymphocytes. Extensive characterization of the precursors by sequential column separation and antibody lysis and also by limiting dilution analysis showed that they were AGM1+ and Lyt 2-; thus they were NK-like cells. In addition to NK-like cells being identified as the precursors, two other cell compartments were identified as ancillary cells which regulate the lymphokine-induced cytotoxicity. They were the macrophages and T-cells. Macrophages were needed to produce CCDF and to activate the Lyt 1+ helper T-cells to produce interleukin 2. The Lyt 2+ T-cells play a negative role in the regulation of the lymphokine-induced cytotoxic cell response. The process of lymphokine-induced cytotoxicity thus involves a complex interaction between at least two lymphokines (interleukin 2 and CCDF) and three cell compartments, namely, NK-like cells, macrophages, and T-cells of Lyt 1+ and Lyt 2+ phenotypes.