TNF-alpha and IFN-gamma reverse IL-4 inhibition of lymphokine-activated killer cell function

Cellular Immunology
S G SwisherS H Golub

Abstract

Recombinant IL-4 inhibits IL-2-induced lymphokine-activated killer (LAK) cell development of PBMC. We evaluated the effect of various cytokines in reversing IL-4-mediated LAK inhibition. PBMC were cultured in IL-2 (10-1000 u/ml) with or without IL-4 (2-100 u/ml) and tested for cytotoxicity against the NK-sensitive K562 cells and NK-resistant UCLA-SO-M14 cells. Addition of IL-4 at the beginning of culture suppresses LAK activity in a dose-dependent fashion. Addition of IFN-gamma or TNF-alpha partially reverses IL-4-mediated inhibition (30-100%) in a dose-dependent fashion. IFN-gamma and TNF-alpha must be added within the first 24 hr of initiating culture in order to reverse IL-4 inhibition. Furthermore, IFN-gamma and TNF-alpha are most effective at reversing IL-4 inhibition at low concentrations of IL-2 (less than 100 u/ml). Addition of other IL-2-induced cytokines such as GM-CSF (50 u/ml), M-CSF (250 u/ml), and IFN-alpha (10-10,000 u/ml) fails to reverse IL-4 inhibition. In addition to suppression of LAK induction, IL-4 also inhibits IL-2-induced IFN-gamma and TNF-alpha protein production in PBMC. The reversal of IL-4-mediated LAK inhibition by TNF-alpha and IFN-gamma may therefore be due to resupply of these endogenously suppr...Continue Reading

References

Jan 1, 1989·Cancer Immunology, Immunotherapy : CII·Y TokudaS H Golub

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Citations

Jan 1, 1991·Cancer Immunology, Immunotherapy : CII·R A LindemannR K Gupta
Aug 1, 1993·Scandinavian Journal of Immunology·S IhoH Shau
Jan 1, 1991·Annals of the New York Academy of Sciences·P RalphA Sampson-Johannes
Feb 1, 1995·European Journal of Haematology·C FeganJ A Whittaker

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