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


ABSTRACT: 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.

SUBMITTER: Ryan JA 

PROVIDER: S-EPMC2919900 | biostudies-other | 2010 Jul

REPOSITORIES: biostudies-other

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

Ryan Jeremy A JA   Brunelle Joslyn K JK   Letai Anthony A  

Proceedings of the National Academy of Sciences of the United States of America 20100706 29


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 demonstr  ...[more]

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