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.
Ting
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CC
Yang
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Hargrove
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ME
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000032:analysis; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D004357:Drug Synergism; D005260:Female; D007376:Interleukin-2 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008222:Lymphokines / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D007376:Interleukin-2; D008222:Lymphokines