HIV Gene Expression Enhances T Cell Susceptibility to Hydrogen Peroxide-Induced Apoptosis

Abstract

A human T cell lineage was used to determine the possible effects of HIV infection on T cell antioxidant status. On inoculation into serum-free culture, 8E5, a constitutive HIV-expressing T cell line, underwent apoptosis whereas cell death was not observed with the uninfected A3.01 or latently HIV-infected 8E5L T cell lines. 8E5 survival was markedly prolonged by supplementing the serum-free medium with either A3.01-conditioned medium, catalase, vitamin E, or 2-mercaptoethanol, but supplementation with ascorbic acid, glutathione, or N-acetylcysteine had no effect. Consistent with their being in a state of oxidative stress, 8E5 cells displayed reduced levels of catalase activity, and were more susceptible to killing by exogenous hydrogen peroxide (H²O²) than A3.01 and 8E5L cells. These results demonstrate an inverse correlation between HIV gene expression and antioxidant status in human T cells. Enhanced cytotoxicity of HIV-infected, antioxidant-deficient CD4 T cells following exposure to H²O² in lymphoid tissues responding to opportunistic pathogens may contribute to the depletion of CD4 T cells in AIDS.