Lahdenpohja N, Hurme M
Department of Microbiology and Immunology, University of Tampere Medical School, Finland.
Cell Immunol. 1996 Nov 1;173(2):282-6. doi: 10.1006/cimm.1996.0279.
Formation of reactive oxygen intermediates (ROI) after oxidative stress has been shown to be an activation signal for T lymphocytes, e.g., expression of IL-2 and its receptor are induced. These ROI-induced effects can, to a large extent, be attributed to the activation of the transcription factor NF-kappaB. Now we have examined whether naive and memory T lymphocytes differ in their sensitivity to ROI-mediated signals. When CD45RA+ (naive) and CD45RO+ (memory) T lymphocytes were directly stimulated with H2O2, NF-kappaB nuclear translocation was stronger in naive cells than in memory cells and it could be induced with lower doses. The composition of the induced nuclear NF-kappaB (levels of p50 and RelA proteins) was similar in these cell types. The magnitude and kinetics of intracellular ROI were similar, suggesting that there were no differences in ROI-forming mechanisms or antioxidative capacities. The probable regulatory point was the cytoplasmic IkappaB inhibitor: in CD45RA+ cells, H2O2 caused a more profound depression in the levels of IkappaB alpha. These findings indicate that T cells representing different activation and/or differentiation stages can be differentially responsive to ROI-mediated signals.
氧化应激后活性氧中间体(ROI)的形成已被证明是T淋巴细胞的激活信号,例如,可诱导白细胞介素-2及其受体的表达。这些ROI诱导的效应在很大程度上可归因于转录因子NF-κB的激活。现在我们研究了初始T淋巴细胞和记忆T淋巴细胞对ROI介导信号的敏感性是否存在差异。当用H2O2直接刺激CD45RA +(初始)和CD45RO +(记忆)T淋巴细胞时,初始细胞中NF-κB的核转位比记忆细胞更强,并且用较低剂量即可诱导。在这些细胞类型中,诱导的核NF-κB的组成(p50和RelA蛋白水平)相似。细胞内ROI的大小和动力学相似,表明ROI形成机制或抗氧化能力没有差异。可能的调控点是细胞质中的IκB抑制剂:在CD45RA +细胞中,H2O2导致IκBα水平更显著的降低。这些发现表明,代表不同激活和/或分化阶段的T细胞对ROI介导的信号可能有不同的反应。