Gupta S, Young T, Yel L, Su H, Gollapudi S
Division of Basic and Clinical Immunology, University of California, Irvine, CA 92697, USA.
Genes Immun. 2007 Oct;8(7):560-9. doi: 10.1038/sj.gene.6364416. Epub 2007 Aug 9.
CD4+ and CD8+ memory T cells are identified into central and effector memory subsets, which are characterized by distinct homing patterns and functions. In this investigation, we show that naïve and central memory CD4+ and CD8+ T cells are sensitive to hydrogen peroxide (H2O2)-induced apoptosis, whereas effector memory CD4+ and CD8+ T cells are relatively resistant to H2O2-induced apoptosis. Apoptosis in naïve and central memory CD4+ and CD8+ is associated with the release of cytochrome c and activation of caspase-9 and caspase-3, upregulation of Bax and voltage-dependent anion channel (VDAC) expression, and decreased intracellular glutathione (GSH). In vitro GSH and a superoxide dismutase mimetic Mn(III) tetrakis (1-methyl-4-pyridyl) porphyrin inhibited H2O2-induced apoptosis in both naïve and central memory CD4+ and CD8+ T cells. Furthermore, VDAC inhibitor 4,4'-diisothiocynostilbene-2,2'-disulfonic acid blocked H2O2-induced apoptosis. These data demonstrate that H2O2 induces apoptosis preferentially in human naïve and central memory CD4+ and CD8+ T cells via the mitochondrial pathway by regulating intracellular GSH and the expression of Bax and VDAC.
CD4+和CD8+记忆性T细胞可分为中枢记忆和效应记忆亚群，它们具有不同的归巢模式和功能。在本研究中，我们发现初始和中枢记忆性CD4+和CD8+ T细胞对过氧化氢（H2O2）诱导的凋亡敏感，而效应记忆性CD4+和CD8+ T细胞对H2O2诱导的凋亡相对抵抗。初始和中枢记忆性CD4+和CD8+ T细胞的凋亡与细胞色素c的释放、caspase-9和caspase-3的激活、Bax和电压依赖性阴离子通道（VDAC）表达的上调以及细胞内谷胱甘肽（GSH）的减少有关。体外实验中，GSH和超氧化物歧化酶模拟物锰（III）四（1-甲基-4-吡啶基）卟啉可抑制H2O2诱导的初始和中枢记忆性CD4+和CD8+ T细胞凋亡。此外，VDAC抑制剂4,4'-二异硫氰基芪-2,2'-二磺酸可阻断H2O2诱导的凋亡。这些数据表明，H2O2通过调节细胞内GSH以及Bax和VDAC的表达，经线粒体途径优先诱导人初始和中枢记忆性CD4+和CD8+ T细胞凋亡。
