Khan Masood A, Sriram Venkataraman, Renukaradhya Gourapura J, Du Wenjun, Gervay-Hague Jacquelyn, Brutkiewicz Randy R
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202-5181, USA.
Immunology. 2008 Sep;125(1):80-90. doi: 10.1111/j.1365-2567.2008.02823.x. Epub 2008 Mar 14.
The stimulation of programmed cell death can either enhance or inhibit antigen presentation by classic major histocompatibility complex molecules. In the current study, we report that the induction of apoptosis by topoisomerase I inhibition or elevation of intracellular ceramide levels substantially impairs CD1d-mediated antigen presentation. In the former case, such a reduction occurred via the regulation of both the p38 mitogen-activated protein kinases and protein kinase C delta signal transduction pathways as well as the caspase cascade, whereas the latter was p38-(but not caspase)-dependent. Confocal microscopic analysis showed an altered intracellular distribution of CD1d following the inhibition topoisomerase I or by an increase in intracellular ceramide levels, that was prevented by p38 and caspase inhibitors. Thus, the induction of apoptosis in antigen presenting cells severely compromises CD1d-mediated antigen presentation by multiple mechanisms.
程序性细胞死亡的刺激作用既可以增强也可以抑制经典主要组织相容性复合体分子介导的抗原呈递。在本研究中，我们报告称，通过抑制拓扑异构酶I或提高细胞内神经酰胺水平诱导凋亡，会显著损害CD1d介导的抗原呈递。在前一种情况下，这种减少是通过p38丝裂原活化蛋白激酶和蛋白激酶Cδ信号转导途径以及半胱天冬酶级联反应的调节而发生的，而后者则依赖于p38（而非半胱天冬酶）。共聚焦显微镜分析显示，在抑制拓扑异构酶I或细胞内神经酰胺水平升高后，CD1d的细胞内分布发生改变，而p38和半胱天冬酶抑制剂可阻止这种改变。因此，抗原呈递细胞中凋亡的诱导通过多种机制严重损害了CD1d介导的抗原呈递。
