ENVIRONMENTAL SIGNALS INFLUENCING EXPRESSION OF THE IFN-GAMMA RECEPTOR ON HUMAN T-CELLS CONTROL WHETHER IFN-GAMMA PROMOTES PROLIFERATION ORAPOPTOSIS

IFN-gammaR expression is subject to contrasting modulation on human T cells. IFN-gammaR constitutive expression is low on three human malign ant T cells (ST4, PF382, and Jurkat) growing in medium supplemented wi th serum. The addition of IFN-gamma down-modulates IFN-gammaR expressi on and increases both proliferation and MHC class I Ag expression. By contrast, when malignant T cells are cultured in medium without serum, IFN-gammaR 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 abil ity of IFN-gamma to stimulate malignant T cell proliferation or death correlates with the intensity of IFN-gammaR cell expression, high expr ession being a marker for cell apoptosis. IFN-gammaR up-modulation als o occurs on malignant T cells undergoing apoptosis after treatment wit h dexamethasone, on irradiated normal CD3+ PBL, and on cultured normal CD3+ thymocytes. Moreover, the ability of IFN-gamma to augment apopto sis of highly IFN-gammaR-positive thymocytes suggests that its role in promoting T cell apoptosis is also important in physiologic condition s.