Changes in intracellular glutathione levels in stimulated and unstimulated lymphocytes in the presence of 2-mercaptoethanol or cysteine.

Certain low m.w. thiol compounds can enhance various in vitro lymphocyte mitogenic responses, whereas reagents that react with sulfhydryl groups are potent cell poisons. The possible targets for thiols and thiol reagents could include membrane and cytoplasmic proteins, some of which may regulate lymphocyte proliferation. As a step toward understanding how lymphocyte proliferation is enhanced in the presence of thiols, we studied the appearance of both protein and non-protein sulfhydryl groups in stimulated lymphocytes. To help clarify the role of the cellular targets for thiols, we studied the time course of appearance of both protein and non-protein sulfhydryl groups as lymphocytes proliferate under various conditions. In the presence of an appropriate concentration of the thiol 2-mercaptoethanol (2-ME), there is a substantial rise in the level of intracellular glutathione for lymphocytes stimulated with the mitogen concanavalin A (Con A). Otherwise, the level of intracellular glutathione declines, even for Con A-stimulated cells, but the presence of 2-ME partially prevents this decline. Increasing the amount of cysteine in the medium to a level that enhances cell proliferation leads to effects similar to those obtained with 2-ME. Thus, apparently one effect of various thiol reducing agents is to enhance the production of glutathione in lymphocyte mitogenesis and to protect against the loss of glutathione that occurs in resting or proliferating lymphocytes.