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.