Differential effects of glutathione depletion on T cell subsets.
Glutathione (GSH) is known to play an important role in various lymphocyte functions. We now report that different T cell subsets express different requirements for intracellular GSH. Depletion of intracellular GSH by buthionine sulfoximine (BSO), a specific inhibitor of GSH biosynthesis, decreases the proportion of CD8+ cells (i.e., increases the CD4+/CD8+ ratio), and inhibits particularly the generation of large blast-like CD8+ cells and cytotoxic T lymphocyte (CTL) activity. CTL activity is restored by administration of exogenous GSH. Differential effects of GSH depletion were also seen at the level of individual T cell clones. The CD4+ helper T cell clone D10.G4.1.HD was found to express a high rate of interleukin 2 (IL-2) dependent DNA synthesis even after severe depletion of intracellular GSH, whereas other T cell clones including the clone 29 were severely inhibited by BSO. The results of these studies suggest that the decreased intracellular GSH levels of HIV-1 seropositive persons are probably not (directly) responsible for the selective depletion of the CD4+ T cell subset but may be responsible for a cellular dysfunction of the CD8+ subset and for the ultimate failure of the CTL to control the viral infection in these patients.
Gmünder
H
H
Division of Immunochemistry, Institute of Immunology and Genetics, German Cancer Research Center, Heidelberg.
Dröge
W
W
D000818:Animals; D019328:Buthionine Sulfoximine; D016516:CD4-CD8 Ratio; D002999:Clone Cells; D004247:DNA / Q000096:biosynthesis; D005978:Glutathione / Q000502:physiology*; D015658:HIV Infections / Q000276:immunology; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D015375:Receptors, Interleukin-2 / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D015375:Receptors, Interleukin-2; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D004247:DNA; D005978:Glutathione