Heightened mitochondrial priming is the basis for apoptotic hypersensitivity of CD4+ CD8+ thymocytes
Heightened mitochondrial priming is the basis for apoptotic hypersensitivity of CD4+ CD8+ thymocytes
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DOI：
10.1073/pnas.0914878107
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发表时间：
2010-07-20
影响因子：
11.1
通讯作者：
Letai, Anthony
中科院分区：
文献类型：
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作者：
Ryan, Jeremy A.;Brunelle, Joslyn K.;Letai, Anthony
已经确定，CD 4（+）CD 8（+）胸腺细胞比CD 4（+）或CD 8（+）单阳性（SP）胸腺细胞对无数死亡刺激更敏感。这种对CD 4（+）CD 8（+）胸腺细胞凋亡的超敏反应背后的机制尚不清楚。为了测试差异是否在于由BCL-2蛋白家族建立的线粒体凋亡预设，我们开发了一种方法，基于FACS的BH 3分析。使用这个工具，我们可以区分胸腺细胞亚群，并证明双阳性（DP）胸腺细胞中的线粒体比单阳性胸腺细胞中的线粒体更容易死亡。已知引起自身免疫的促凋亡BIM的丧失也引起“启动”的丧失。“引发是一种具有生理后果的表型，可以使用基于FACS的BH 3分析在复杂样品中的单细胞水平上进行测量。
It is well established that CD4(+) CD8(+) thymocytes are more sensitive to myriad death stimuli than CD4(+) or CD8(+) single positive (SP) thymocytes. The mechanism behind this hypersensitivity to apoptosis of CD4(+) CD8(+) thymocytes is not understood. To test whether the difference lay in the apoptotic preset of mitochondria, established by the BCL-2 family of proteins, we developed a method, FACS-based BH3 profiling. Using this tool, we could discriminate thymocyte subpopulations and demonstrate that mitochondria in double positive (DP) thymocytes are more primed for death than those in single positive counterparts. Loss of proapoptotic BIM, known to cause autoimmunity, also causes loss of "priming." Priming is a phenotype with physiologic consequences, which can be measured at the single-cell level in complex samples using FACS-based BH3 profiling.