Environmental signals influencing expression of the IFN-gamma receptor on human T cells control whether IFN-gamma promotes proliferation or apoptosis.
IFN-gamma R expression is subject to contrasting modulation on human T cells. IFN-gamma R constitutive expression is low on three human malignant T cells (ST4, PF382, and Jurkat) growing in medium supplemented with serum. The addition of IFN-gamma down-modulates IFN-gamma R expression and increases both proliferation and MHC class I Ag expression. By contrast, when malignant T cells are cultured in medium without serum, IFN-gamma R expression dramatically increases and the cells undergo a slow apoptotic death. The addition of IFN-gamma enhances apoptosis and inhibits cell rescue in serum-supplemented medium. This opposite ability of IFN-gamma to stimulate malignant T cell proliferation or death correlates with the intensity of IFN-gamma R cell expression, high expression being a marker for cell apoptosis. IFN-gamma R up-modulation also occurs on malignant T cells undergoing apoptosis after treatment with dexamethasone, on irradiated normal CD3+ PBL, and on cultured normal CD3+ thymocytes. Moreover, the ability of IFN-gamma to augment apoptosis of highly IFN-gamma R-positive thymocytes suggests that its role in promoting T cell apoptosis is also important in physiologic conditions.
Novelli
F
F
CNR-Immunogenetics and Histocompatibility Center, University of Turin, Italy.
Di Pierro
F
F
Francia di Celle
P
P
Bertini
S
S
Affaticati
P
P
Garotta
G
G
Forni
G
G
D017209:Apoptosis; D003470:Culture Media; D004249:DNA Damage; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000502:physiology*; D008213:Lymphocyte Activation; D017471:Receptors, Interferon / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology*; D013950:Thymus Gland / Q000166:cytology; D014407:Tumor Cells, Cultured; D000096743:Interferon gamma Receptor
D003470:Culture Media; D007371:Interferon-gamma; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor