In vitro induction of tumoricidal and suppressor macrophages by lymphokines: Possible feedback regulation

D. Taramelli, H. T. Holden, L. Varesio

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Proteose-peptone-induced macrophages (pM∅) from C57BL/6 (B6) mice were treated in vitro with lymphokine, and 2 functions were evaluated: the ability to suppress lymphokine production and the cytotoxic capacity against tumor target cells. When 10% to 20% pM∅ treated with lymphokine were added to a lymphokine-producing system, strong inhibition of MIF and MAF production occurred. The suppression was not specific, since pM∅ inhibited the production of lymphokine obtained by either mitogenic stimulation of normal spleen cells (NSC) or alloantigen stimulation of immune spleen cells (ISC). The suppressor cells were adherent, phagocytic, Thy 1.2 negative, with monocyte-macrophage-like morphology. Lymphokine-treated pM∅ were also tumoricidal when tested in 18 hr microcytotoxicity assay against RL♂1 lymphoma target cells. However, using endotoxin-free reagents (≤0.01 ng/ml of endotoxin by the LAL assay), we found that small amounts of lipopolysaccharide (LPS) were required, in addition to lymphokine, to induce tumoricidal activity in pM∅. In contrast, noncytotoxic pM∅ stimulated with lymphokine alone were also able to inhibit lymphokine production, although not as effectively as pM∅ stimulated by lymphokine plus LPS. Therefore, we concluded that lymphokine treatment itself is sufficient to induce M∅ to become suppressor cells, whereas an additional signal is necessary to induce cytolytic activity. We suggest that there is a negative feedback mechanism of control on the lymphokine-producing cells through the activation of suppressor M∅ by lymphokine.

Original languageEnglish
Pages (from-to)2123-2128
Number of pages6
JournalJournal of Immunology
Issue number6
Publication statusPublished - 1981

ASJC Scopus subject areas

  • Immunology


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