Identification of Components of Differentiation-Inducing Activity of Human T-Cell Lymphoma Cells by Induction of Differentiation in Human Myeloid Leukemia Cells

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Abstract
Two lymphokines that contribute to induction of cell differentiation in promyelocytic HL-60 leukemia cells by human T-cell lymphoma HUT-102 cells were identified previously. The lymphokines identified in the differentiation-inducing preparation were interferon-7(IFN-7) and lym-photoxin. To determine the remaining component(s) of this differentiation-inducing activity, we used gene-cloned (recombinant) forms and antibodies of lymphokines. The differentiation-inducing activity of the HUT-102 cells was not completely neutralized by the antibodies, suggesting that an additional lymphokine(s) is involved. Granulocyte-macrophage colony-stimulating factor (GM-CSF) in combination with retinoic acid induced differentiation of the HL-60 cells in a dose-dependent manner. Furthermore, the activity of the differentiation-inducing factors was partially inhibited by anti-GM-CSF antibody and completely inhibited by the combination of antibodies to lymphotoxin, IFN-γ, and GM-CSF. These results indicate that, in addition to IFN-γ and lymphotoxin, GM-CSF is the third major component released by HUT-102 cells for inducing differentiation of HL-60 cells. [J Natl Cancer Inst 81:952-956, 1989]