Interleukin 2 induces human acute lymphocytic leukemia cells to manifest lymphokine-activated-killer (LAK) cytotoxicity.
Lymphokine-activated killer cells (LAK) were originally distinguished from natural killers (NK) and cytotoxic T lymphocytes. Recently, however, IL 2-activated NK cells were suggested as the major source of LAK reactivity in human peripheral blood (PBL). Because certain T cell acute lymphoblastic leukemia (T-ALL) cells are phenotypically similar to LAK precursors, we have asked whether these leukemic cells can be induced toward LAK-cytotoxicity and express NK reactivity before stimulation. Five out of seven T-ALL preparations were induced by IL 2 to kill target cells. The cytotoxicity of the leukemic-LAK cells resembled that of normal LAK effectors as they lysed efficiently the NK-resistant target Daudi, as well as fresh human sarcoma, carcinoma, and renal cancer cells but not normal PBL. The ALL-LAK precursors phenotype was T3-, T4-, T8-, and T11+, similar to most normal LAK precursors. In contrast to normal PBL that generated LAK effectors when their proliferation was inhibited, the irradiated, nonproliferating T-ALL leukemic cells did not respond to IL 2. Therefore, the T-ALL LAK cytotoxicity was attributed to the leukemic cells rather than to residual normal lymphocytes. The IL 2-responding T-ALL cells did not express autonomous NK type cytotoxicity, suggesting that they reflect LAK precursors of non-NK origin. The homogeneous leukemic preparations with inducible LAK cytotoxicity described herein provide a model system for studying normal LAK cells.
D002454:Cell Differentiation / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D007945:Leukemia, Lymphoid / Q000473:pathology*; D008213:Lymphocyte Activation / Q000187:drug effects; D010641:Phenotype; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000145:classification / Q000187:drug effects
D007376:Interleukin-2; D011994:Recombinant Proteins