The different effects of recombinant human interferon-.GAMMA. and recombinant human interferon-.BETA. on the activation of natural killer cells.
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Highly purified recombinant human interferon-γ produced by Escherichia coli (ReIFN-γ) was examined for ability to stimulate natural killer (NK) cell cytotoxic activity and antibody-dependent cell-mediated cytotoxicity in human peripheral blood lymphocytes (PBLs) in comparison with natural human interferon-γ (IFN-γ) and with recombinant human interferon-β produced by E. coli (ReIFN-β). The activity of ReIFN-γ to stimulate NK cell cytotoxicity was about 10 times greater than that of ReIFN-β and similar to that of IFN-γ when PBLs were pretreated with each interferon for 16hr. The effects of ReIFN-γ were completely neutralized by a rabbit anti-ReIFN-γ antibody, but not by a rabbit anti-ReIFN-β. ReIFN-γ did not show any significant NK-enhancing effect when it was added directly to the killing phase of standard 51Cr-release assay for 4hr, while ReIFN-β showed a marked effect. The time course study showed that the NK-activating effect of ReIFN-γ was not expressed until 2hr after the start of incubation, while that of ReIFN-β was expressed rapidly and sufficiently within 15min. This kinetic difference between ReIFN-γ and ReIFN-β was confirmed by an experiment using the Ca2+-pulse method, in which the killing rate in the Ca2+-dependent stage of NK cytolysis was increased by ReIFN-γ, but only after 6hr of preincubation, while the effect by ReIFN-β was expressed rapidly at 30min. These findings suggest that ReIFN-γ and ReIFN-β may stimulate NK cell cytotoxicity through different intracellular events after they bind to their receptors on the surface of NK cells.
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