Intracellular Glutathione Levels in T Cell Subsets Decrease in HIV-Infected Individuals

Abstract

The authors have shown previously that intracellular glutathione (GSH) plays an important role in the regulation of human immunodeficiency virus (HIV) transcription and replication in vitro, through modulation of signal transduction by inflammatory cytokines. Moreover, intracellular GSH levels are known to regulate T-lymphocyte function. In multiparameter FACS studies presented here, we show that relative GSH levels in CD4⁺ and CD8⁺ T cells from HIV⁺ individuals are significantly lower than in corresponding subsets from uninfected controls. These studies define the relative intracellular glutathione (GSH) levels in CD4⁺ T cells, CD8⁺ T cells, B cells, and monocytes from 134 HIV-infected individuals and 31 uninfected controls. The greatest decreases in intracellular GSH occur in subsets of T cells in individuals in the later stages of the HIV infection. In AIDS patients, GSH levels are 63% of normal in CD4+ T cells (p < 0.0001) and are 62% of normal in CD8+ T cells (p < 0.0001). Similarly, in AIDS-related complex (ARC) patients, GSH levels are 66% of normal in CD4⁺ T cells (p < 0.003) and are 69% of normal in CD8⁺ T cells (p < 0.003). These findings suggest that low intracellular GSH levels may be an important factor in HIV infection and in the resulting immunodeficiency.