Redox signals and NF-κB activation in T cells

Accumulating data from a number of laboratories have recently indicated that the response of transcription factor NF-kappa B to alterations in the redox homeostasis of cells may play an important role in modulating immune function. The activation of NK-kappa B has been recognized to regulate a number of genes necessary for normal T cell responses including IL-2, IL-6, IL-8, and several T cell surface receptors. Diminished NF-kappa B activity has been shown to occur in T cells with aging, suggesting that impaired activation of NF-kappa B might occur juring cellular senescence. In addition, aberrancies in NF-kappa B activity have been implicated in the immunopathogenesis of diseases involving immune or inflammatory processes such as atherosclerosis and HIV-1 infection. The role of H2O2 and other reactive oxygen species (ROS) as an integratory secondary messenger for divergent T cell signals has been complicated by the fact that various T cell lines and peripheral blood T cells differ markedly in the levels of NF-kappa B activation induced by oxidant stress. Additionally. proposed pathways of NF-kappa B activation have been based on indirect evidence provided by experiments which used antioxidants to inhibit active NF-kappa B formation. Further, complete activation of T cells requires at least two signals, one that stimulates an increase in intracellular calcium and one that stimulates enzymatic processes including kinases. Similarly, substantial evidence indicates that full activation of NF-kappa B requires dual signals. The ability of H2O2 or other ROS to induce T cell signals and functional responses by these two mechanisms is reviewed and the specific response of NF-kappa B to redox changes in T cells is examined. Data an also presented to suggest that the redox regulation in NF-kappa B activation may be relevant to immune-related diseases and to aging. (C) 1998 Elsevier Science Inc.