The effect of various cytokines on the in vitro induction of antibody-dependent cellular cytotoxicity in murine cells. Enhancement of IL-2-induced antibody-dependent cellular cytotoxicity activity by IL-1 and tumor necrosis factor-α

A. Eisenthal, S. A. Rosenberg

Research output: Contribution to journalArticlepeer-review

Abstract

We have previously demonstrated that incubation with IL-2 can induce ADCC activty in murine cells and that this activity was mediated by asialo GM1+, FcR+ cells. In the present study we show that the cytokines IFN-α and IFN-γ, TNF-α, and IL-1α are unable to induce antibody-dependent cellular cytotoxicity (ADCC) in murine cells; however, TNF-α and IL-1α could substantially augment the ADCC induced by IL-2. IL-1 increased the IL-2-induced ADCC activity in a dose-dependent fashion and in cells isolated from the thymus and spleen. The precursors of the ADCC induced by the combination of IL-1 and IL-2 were asialo GM1+ cells, similar to the precursor cells of IL-2-induced ADCC. The effect of IL-1 and TNF on ADCC was not the result of an increase in the FcR density on the cell surface or the result of an increase in the number of FcR+ cells although IL-1 increased the recovery of viable cells in culture. The main effect of IL-1 and TNF was the enhancement of the lytic ability of the IL-2 cultured cells as indicated by increased intra-cellular benzyloxycarbonyl L-lysine thiobenzylester-esterase activity. These results suggest that lymphokines such as IL-1 and TNF may synergize with IL-2 in the induction of ADCC and could thus potentially be useful for the immunotherapy of established tumors when combined with the administration of specific anti-tumor antibodies.

Original languageEnglish (US)
Pages (from-to)2307-2313
Number of pages7
JournalJournal of Immunology
Volume142
Issue number7
StatePublished - Jan 1 1989

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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