Interleukin-2 mRNA expression, lymphokine production and DNA synthesis in glutathione-depleted T cells

• Published in: Cellular immunology Vol. 130; no. 2; pp. 520 - 528
• Main Authors: Gmünder, Helmut, Roth, Steffen, Eck, Hans-Peter, Gallas, Heidrun, Mihm, Sabine, Dröge, Wulf
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 15.10.1990; Elsevier
• Subjects: Animals; Biological and medical sciences; Cell Line; Concanavalin A - pharmacology; DNA Replication; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Glutathione - physiology; Immunobiology; Interleukin-2 - biosynthesis; Interleukin-2 - genetics; Lymphocyte Activation - drug effects; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation; Mice; Mice, Inbred C3H; RNA, Messenger - biosynthesis; T-Lymphocytes - metabolism; Cell proliferation; Cell culture; Rodentia; Cytokine; Biosynthesis; Vertebrata; Mammalia; Depletion; Cell line; Messenger RNA; Interleukin 2; Mouse; DNA; Blotting assay; T-Lymphocyte; Mitogen; Intracellular; Growth factor; Glutathione
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1016/0008-8749(90)90292-Y

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 m M) 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 responses may operate best at intermediate GSH levels that are not too high to inhibit IL-2 production but sufficient to support DNA synthesis.