Transforming Growth Factor-β Inhibits Interferon-γ Secretion by Lymph okine-activated Killer Cells Stimulated with Tumor Cells

The effect of transforming growth factor-β(TGF-β) secreted by glioblastoma (T98G) cells on the secretion of interferon-γ(IFN-γ) by lymphokine-activated killer (LAK) cells stimulated with tumor cells was investigated in cocultures of LAK and Daudi cells supplemented with T98G culture supernatant, T98G culture supernatant preincubated with anti-TGF-β1 and anti-TGF-β2 neutralizing antibodies, anti-TGF-β1 and anti-TGF-β2 antibodies, or natural human TGF-β1 or recombinant human TGF-β2. LAK cells were incubated with anti-TGF-β1 and anti-TGF-β2 antibodies, and with T98G cells of which the supernatant contained both active and latent forms of TGF-β1 and TGF-β2, with or without neutralizing antibodies. Addition of the supernatant from T98G cells to LAK/Daudi culture caused inhibition of IFN-γ secretion by LAK cells. The inhibition was abolished by pretreatment of the supernatants with anti-TGF-β antibodies. Addition of TGF-β1 and TGF-β2 to the LAK/Daudi culture inhibited IFN-γ secretion by LAK cells in a dose-dependent manner. Addition of anti-TGF-β antibodies to the LAK culture resulted in increased IFN-γ secretion. T98G cells failed to stimulate LAK cells to secrete more IFN-γ. Addition of anti-TGF-β antibodies to the LAK-T98G culture resulted in increased IFN-γ secretion by LAK cells. These results suggest that most malignant glioma cells which secrete high levels of TGF-β can inhibit IFN-γ secretion by LAK cells even after tumor cell stimulation.