Loss of BIM in T cells results in BCL-2 family BH3-member compensation but incomplete cell death sensitivity normalization.
Apoptosis
; 25(3-4): 247-260, 2020 04.
Article
en En
| MEDLINE
| ID: mdl-31993851
ABSTRACT
BIM is the master BH3-only BCL-2 family regulator of lymphocyte survival. To understand how long-term loss of BIM affects apoptotic resistance in T cells we studied animals with T cell-specific deletion of Bim. Unlike CD19CREBimfl/fl animals, LCKCREBimfl/fl mice have pronounced early lymphocytosis followed by normalization of lymphocyte counts over time. This normalization occurred in mature T cells, as thymocyte development and apoptotic sensitivity remained abnormal in LCKCREBimfl/fl mice. T cells from aged mice experienced normalization of their absolute cell numbers and responses against various apoptotic stimuli. mRNA expression levels of BCL-2 family proteins in CD4+ and CD8+ T cells from young and old mice revealed upregulation of several BH3-only proteins, including Puma, Noxa, and Bmf. Despite upregulation of various BH3 proteins, there were no differences in anti-apoptotic BCL-2 protein dependency in these cells. However, T cells had continued resistance to direct BIM BH3-induced mitochondrial depolarization. This study further highlights the importance of BIM in cell death maintenance in T cells and provides new insight into the dynamism underlying BH3-only regulation of T cell homeostasis versus induced cell death and suggests that CD4+ and CD8+ T cells compensate differently in response to loss of Bim.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Linfocitos T
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Muerte Celular
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Proteínas Proto-Oncogénicas c-bcl-2
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Proteína 11 Similar a Bcl2
Tipo de estudio:
Diagnostic_studies
Límite:
Animals
Idioma:
En
Año:
2020
Tipo del documento:
Article