Transforming growth factor-beta inhibits interferon-gamma secretion by lymphokine-activated killer cells stimulated with tumor cells.
The effect of transforming growth factor-beta (TGF-beta) secreted by glioblastoma (T98G) cells on the secretion of interferon-gamma (IFN-gamma) 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-beta 1 and anti-TGF-beta 2 neutralizing antibodies, anti-TGF-beta 1 and anti-TGF-beta 2 antibodies, or natural human TGF-beta 1 or recombinant human TGF-beta 2. LAK cells were incubated with anti-TGF-beta 1 and anti-TGF-beta 2 antibodies, and with T98G cells of which the supernatant contained both active and latent forms of TGF-beta 1 and TGF-beta 2, with or without neutralizing antibodies. Addition of the supernatant from T98G cells to LAK/Daudi culture caused inhibition of IFN-gamma secretion by LAK cells. The inhibition was abolished by pretreatment of the supernatants with anti-TGF-beta antibodies. Addition of TGF-beta 1 and TGF-beta 2 to the LAK/Daudi culture inhibited IFN-gamma secretion by LAK cells in a dose-dependent manner. Addition of anti-TGF-beta antibodies to the LAK culture resulted in increased IFN-gamma secretion. T98G cells failed to stimulate LAK cells to secrete more IFN-gamma. Addition of anti-TGF-beta antibodies to the LAK-T98G culture resulted in increased IFN-gamma secretion by LAK cells. These results suggest that most malignant glioma cells which secrete high levels of TGF-beta can inhibit IFN-gamma secretion by LAK cells even after tumor cell stimulation.
Naganuma
H
H
Department of Neurosurgery, Yamanashi Medical University.
Sasaki
A
A
Satoh
E
E
Nagasaka
M
M
Nakano
S
S
Isoe
S
S
Tasaka
K
K
Nukui
H
H
D001932:Brain Neoplasms / Q000378:metabolism*; D005909:Glioblastoma / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000378:metabolism*; D008222:Lymphokines / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000378:metabolism
D008222:Lymphokines; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma