Open AccessInhibition of Tumor Necrosis Factor‐α and β Secretion by Lymphokine Activated Killer Cells by Transforming Growth Factor‐β
Author(s) -
Naganuma Hirofumi,
Sasaki Atsushi,
Satoh Eiji,
Nagasaka Mitsuyasu,
Nakano Shin,
Isoe Shiro,
Tasaka Kachio,
Nukui Hideaki
Publication year - 1994
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1994.tb02974.x
Subject(s) - lymphokine activated killer cell , lymphokine , secretion , tumor necrosis factor alpha , cell culture , antibody , interleukin 2 , transforming growth factor beta , biology , transforming growth factor , cytokine , microbiology and biotechnology , in vitro , immunology , cytotoxic t cell , interleukin 12 , endocrinology , immune system , biochemistry , genetics
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‐ β l and ‐ β 2 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‐/ β 1 and TGF‐ β 2, 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‐TGF β ‐ 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.