Glutathione regulates interleukin-2 activity on cytotoxic T-cells.
In this study, we examined whether and how the cellular activity of interleukin-2 (IL-2) is affected by glutathione (GSH), an important tripeptide existing in most cells. Cell culture and thymidine incorporation assay showed that addition of GSH enhanced the effect of IL-2 on the proliferation and thymidine incorporation of IL-2-dependent cytotoxic T-cells such as CTLL-2 and CT-4R. Treatment of the cells with GSH resulted in a 2-fold increase in the amount of IL-2 bound to the cells and a rapid internalization of the bound IL-2. In addition, the degradation of IL-2 in the cells was enhanced by GSH treatment. These effects of GSH were accompanied by an increase in the intracellular GSH level. L-Buthionine-(S,R)-sulfoximine, an inhibitor of de novo GSH synthesis, blunted the increase of intracellular GSH level and modulated the effect of GSH on IL-2 activity. These results suggest that GSH regulates the binding, internalization, degradation, and T-cell proliferative activity of IL-2; alterations of cellular GSH concentration may thus affect the growth and replication of IL-2-sensitive cytotoxic T-cells.
Liang
C M
CM
Division of Blood and Blood Products, Food and Drug Administration, Bethesda, Maryland.
Lee
N
N
Cattell
D
D
Liang
S M
SM
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D019328:Buthionine Sulfoximine; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects; D005978:Glutathione / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D007700:Kinetics; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000187:drug effects / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*; D013936:Thymidine / Q000378:metabolism
D000963:Antimetabolites; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D005978:Glutathione; D013936:Thymidine