Interleukin-2 mRNA expression, lymphokine production and DNA synthesis in glutathione-depleted T cells.
The stimulation of DNA synthesis in lymphocyte populations was previously shown to depend strongly on the intracellular glutathione (GSH) level. Since T cell growth is known to depend on interleukin 2 (IL-2), the experiments in this report were designed to determine whether intracellular GSH depletion may inhibit IL-2 production or the IL-2 dependent DNA synthesis. Our experiments revealed that IL-2 production and DNA synthesis of mitogenically stimulated splenic T cells have indeed different requirements for GSH. The addition of relatively high concentrations of GSH (5 mM) to cultures of concanavalin A (Con A)-stimulated splenic T cells was found to augment strongly the DNA synthesis but inhibited the production of IL-2. Moderate intracellular GSH levels, however, are apparently not inhibitory for IL-2 production, since intracellular GSH depletion by cysteine starvation or by graded concentrations of DL-buthionine sulfoximine (BSO) had virtually no effect on IL-2-specific mRNA expression and the production of T cell growth factor (TCGF). The DNA synthesis activity, in contrast, was strongly suppressed after GSH depletion with either method. As in cultures of splenic T cells, GSH depletion had no substantial effect on the induction of IL-2 mRNA and TCGF production in several mitogenically stimulated T cell clones. Taken together, our experiments suggest that complex immune response may operate best at intermediate GSH levels that are not too high to inhibit IL-2 production but sufficient to support DNA synthesis.
Institute of Immunology and Genetics, German Cancer Research Center, Heidelberg.
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D000818:Animals; D002460:Cell Line; D003208:Concanavalin A / Q000494:pharmacology; D004261:DNA Replication; D005978:Glutathione / Q000502:physiology*; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D012333:RNA, Messenger / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000378:metabolism*
D007376:Interleukin-2; D012333:RNA, Messenger; D003208:Concanavalin A; D005978:Glutathione