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Lymphokine-induced Cytotoxicity: Characterization of Effectors, Precursors, and Regulatory Ancillary Cells

Immunology Branch [C-C. T., M. E. H.] and Laboratory of Cellular Oncology [S. S. Y.], National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20205

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 interieukin 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 interieukin 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.

¹ To whom requests for reprints should be addressed, at Immunology Branch, Bldg. 10, Rm. 4B17, National Institutes of Health, Bethesda, MD 20205.

Received 8/19/85. Revised 10/28/85. Accepted 11/ 1/85.