Gupta Sudhir, Su Houfen, Bi Ruifen, Gollapudi Sastry
Division of Basic and Clinical Immunology, University of California, Irvine, California 92697, USA.
J Clin Immunol. 2006 May;26(3):193-203. doi: 10.1007/s10875-006-9019-1. Epub 2006 Jun 2.
In this investigation, we have examined the relative sensitivity of human naïve, central memory (T(CM)), and two types of effector memory CD8+ T cells (T(EM) and T(EMRA)) to TNF-alpha-induced apoptosis. Our data show that naïve and T(CM) CD8+ T cells were sensitive, whereas T(EM) and T(EMRA) CD8+ T cells were relatively resistant to TNF-alpha-induced apoptosis. The apoptosis profile correlated with the activation of caspase-8 and caspase-3. However, no correlation was observed between relative sensitivity of four CD8+ T cell subsets to apoptosis and the expression of TNFR-I or TNFR-II. T(EM) and T(EMRA) CD8+ T cells displayed increased phosphorylation of IKKalpha/beta and IkappaB and increased NF-kappaB activity as compared to naïve and T(CM) CD8+ T cells. Bcl-2, Bcl-x(L) and FLIP(L) expression was higher and Bax expression was lower in T(EM) and T(EMRA) CD8+ T cells as compared to naïve and T(CM) CD8+ T cells. These data suggest that signaling molecules downstream of TNFRs may be responsible for differential sensitivity among subsets of CD8+ T cells to TNF-alpha-induced apoptosis.
在本研究中，我们检测了人类初始型、中枢记忆型（T(CM)）以及两种效应记忆型CD8+ T细胞（T(EM)和T(EMRA)）对肿瘤坏死因子-α（TNF-α）诱导的凋亡的相对敏感性。我们的数据表明，初始型和T(CM) CD8+ T细胞敏感，而T(EM)和T(EMRA) CD8+ T细胞对TNF-α诱导的凋亡相对抵抗。凋亡情况与半胱天冬酶-8（caspase-8）和半胱天冬酶-3（caspase-3）的激活相关。然而，未观察到四个CD8+ T细胞亚群对凋亡的相对敏感性与肿瘤坏死因子受体-I（TNFR-I）或肿瘤坏死因子受体-II（TNFR-II）的表达之间存在相关性。与初始型和T(CM) CD8+ T细胞相比，T(EM)和T(EMRA) CD8+ T细胞显示出IκB激酶α/β（IKKα/β）和IκB的磷酸化增加以及核因子κB（NF-κB）活性增强。与初始型和T(CM) CD8+ T细胞相比，T(EM)和T(EMRA) CD8+ T细胞中Bcl-2、Bcl-x(L)和FLIP(L)的表达较高，而Bax的表达较低。这些数据表明，肿瘤坏死因子受体下游的信号分子可能是CD8+ T细胞亚群对TNF-α诱导凋亡敏感性差异的原因。
Zotero 插件