Human glioma-derived interleukin-10 inhibits antitumor immune responses in vitro.
Intracranial malignant gliomas are sequestered from the immune system yet are associated with broad suppression of host immunocompetence. Immune system dysfunction in patients with gliomas seems to be related to inhibitory mediators produced by glioma cells. We investigated the physiological roles of glioma-derived interleukin (IL)-10 in Class II expression of monocytes, cytokine secretion from lymphocytes, and T cell proliferation in vitro. We could detect the messenger ribonucleic acid transcript of IL-10 in four gliomas by the reverse-transcribed polymerase chain reaction. Glioma-derived IL-10 greatly down-regulated human lymphocyte antigens-DR expression on monocytes. The inhibitory effect of IL-10 on interferon-gamma and tumor necrosis factor-alpha was neutralized by the anti-IL-10 monoclonal antibody; however, the inhibitory effect on IL-2 was not neutralized. Next, supernatants of glioma cells remarkably suppressed T cell proliferation in a dose-dependent fashion; however, this inhibitory effect was not restored by adding anti-IL-10 monoclonal antibodies. The supernatant also inhibited the allocytolytic activity of lymphocytes that were not neutralized by anti-IL-10 monoclonal antibody. IL-10 plays an important role in cytokine synthesis; nevertheless, impaired T cell responsiveness cannot be solely explained by glioma-derived IL-10.
Hishii
M
M
Department of Neurosurgery, Juntendo University School of Medicine, Tokyo, Japan.
Nitta
T
T
Ishida
H
H
Ebato
M
M
Kurosu
A
A
Yagita
H
H
Sato
K
K
Okumura
K
K
D001932:Brain Neoplasms / Q000276:immunology*; D002460:Cell Line; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000502:physiology; D015536:Down-Regulation / Q000502:physiology; D005909:Glioblastoma / Q000276:immunology*; D005910:Glioma / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D016753:Interleukin-10 / Q000502:physiology*; D008213:Lymphocyte Activation / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000276:immunology*
D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D016753:Interleukin-10