Heightened mitochondrial priming is the basis for apoptotic hypersensitivity of CD4+ CD8+ thymocytes

JA Ryan, JK Brunelle, A Letai - Proceedings of the National …, 2010 - National Acad Sciences
JA Ryan, JK Brunelle, A Letai
Proceedings of the National Academy of Sciences, 2010National Acad Sciences
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 …
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.
National Acad Sciences