Hamilos D L, Mascali J J, Wedner H J
National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
Int J Immunopharmacol. 1991;13(1):75-90. doi: 10.1016/0192-0561(91)90028-6.
Depletion of intracellular glutathione (GSH) inhibits the lectin-induced activation response of human T lymphocytes. GSH-depleted lymphocytes undergo a partial activation response to lectins but fail to undergo blast transformation. Several lines of evidence indicate that the inhibition of lymphocyte activation in GSH-depleted lymphocytes involves relatively late activation events. Firstly, lectin stimulation induces significant 14C-AIB uptake, IL-2 production and expression of IL-2 receptor but a near complete inhibition of 3H-uridine and 3H-thymidine incorporation. Comparable levels of IL-2 production and IL-2 receptor expression are seen in GSH-depleted lymphocytes allowed to recover from GSH depletion during lectin stimulation. However, in the latter case, 3H-uridine and 3H-thymidine incorporation are normal, and activation is completely restored. Exogenous IL-2 cannot restore activation in GSH-depleted lymphocytes. Furthermore, lymphocytes remain highly susceptible to inhibition by GSH depletion even after 48 h of lectin stimulation which is sufficient to induce early activation events in the Go----G1 transition, such as IL-2 receptor expression and IL-2 production. Exogenous GSH partially restores intracellular GSH levels and completely restores lymphocyte activation in GSH-depleted lymphocytes. Despite comparable degrees of GSH depletion, DL-buthionine-SR-sulfoximine and 2-cyclohexene-1-one inhibit lymphocyte activation to different degrees. The inhibition by 2-cyclohexene-1-one is consistently greater than would be predicted based on glutathione depletion per se. We conclude that GSH-dependent processes are important in relatively late steps of the activation sequence characterized by nuclear events with relative sparing of essential early steps in activation, such as IL-2 receptor expression and IL-2 production. The approximate minimal intracellular GSH concentration necessary to sustain a normal activation response is 2 nmol per 10(7) lymphocytes.
细胞内谷胱甘肽（GSH）的耗竭会抑制人T淋巴细胞的凝集素诱导激活反应。GSH耗竭的淋巴细胞对凝集素会产生部分激活反应，但无法发生母细胞转化。多项证据表明，GSH耗竭淋巴细胞中淋巴细胞激活的抑制涉及相对较晚的激活事件。首先，凝集素刺激会诱导显著的14C-AIB摄取、IL-2产生和IL-2受体表达，但对3H-尿苷和3H-胸苷掺入几乎完全抑制。在凝集素刺激期间从GSH耗竭中恢复的GSH耗竭淋巴细胞中可观察到相当水平的IL-2产生和IL-2受体表达。然而，在后一种情况下，3H-尿苷和3H-胸苷掺入正常，激活完全恢复。外源性IL-2无法恢复GSH耗竭淋巴细胞的激活。此外，即使在凝集素刺激48小时后，淋巴细胞仍对GSH耗竭高度敏感，而48小时的凝集素刺激足以诱导Go----G1期转换中的早期激活事件，如IL-2受体表达和IL-2产生。外源性GSH可部分恢复细胞内GSH水平，并完全恢复GSH耗竭淋巴细胞中的淋巴细胞激活。尽管GSH耗竭程度相当，但DL-丁硫氨酸-SR-亚砜胺和2-环己烯-1-酮对淋巴细胞激活的抑制程度不同。2-环己烯-1-酮的抑制作用始终大于基于谷胱甘肽耗竭本身所预测的程度。我们得出结论，GSH依赖性过程在激活序列的相对较晚步骤中很重要，这些步骤以核事件为特征，而激活的基本早期步骤，如IL-2受体表达和IL-2产生，相对未受影响。维持正常激活反应所需的细胞内GSH近似最低浓度为每10(7)个淋巴细胞2 nmol。
