Inhibition of Tumor Necrosis Factor‐α and β Secretion by Lymphokine Activated Killer Cells by Transforming Growth Factor‐β

Transforming growth factor-β (TGF-β) has a variety of immunosuppressive properties. We investigated the effect of TGF-β secreted by glioblastoma (T98G) cells on the secretion of tumor necrosis factor-α and -β (TNFs) by lymphokine activated killer (LAK) cells stimulated with tumor cells. The supernatant from T98G cells was preincubated with anti-TGF-βl and -β2 neutralizing antibodies or untreated, and added to a coculture of LAK and Daudi cells. The neutralizing antibodies were added to LAK/Daudi and LAK culture, and natural human TGF-β and recombinant human TGF-β were also added to the LAK/Daudi culture. LAK cells were also cultured with T98G cells, of which the supernatant contained both active and latent forms of TGF-/β1 and TGF-β2, and the neutralizing antibodies were added to the coculture. TNFs activity in the supernatants from LAK/ Daudi cultures was examined by a specific bioassay. Addition of the supernatant from T98G cells to LAK/Daudi culture resulted in the inhibition of TNFs secretion by LAK cells. The inhibition was abrogated by the pretreatment of the supernatants with the anti-TGF-β antibodies. Addition of TGF-β and TGF-β to LAK/Daudi culture inhibited TNFs secretion by LAK cells in a dose-dependent manner. Addition of anti-TGFβ- antibodies to LAK culture resulted in an increase of TNFs secretion. These results suggest that, if tumor cells have the capacity to convert TGF-β from a latent to an active form, the active TGF-β suppresses TNFs secretion by LAK cells stimulated with the tumor cells, and that TGF-β secreted and activated by glioblastoma cells suppresses the propagation of immune reaction by inhibiting TNFs secretion by activated lymphocytes adjacent to tumor cells.