Intrinsic role of FoxO3a in the development of CD8+ T cell memory.
J Immunol
; 190(3): 1066-75, 2013 Feb 01.
Article
en En
| MEDLINE
| ID: mdl-23277488
ABSTRACT
CD8(+) T cells undergo rapid expansion during infection with intracellular pathogens, which is followed by swift and massive culling of primed CD8(+) T cells. The mechanisms that govern the massive contraction and maintenance of primed CD8(+) T cells are not clear. We show in this study that the transcription factor, FoxO3a, does not influence Ag presentation and the consequent expansion of CD8(+) T cell response during Listeria monocytogenes infection, but plays a key role in the maintenance of memory CD8(+) T cells. The effector function of primed CD8(+) T cells as revealed by cytokine secretion and CD107a degranulation was not influenced by inactivation of FoxO3a. Interestingly, FoxO3a-deficient CD8(+) T cells displayed reduced expression of proapoptotic molecules BIM and PUMA during the various phases of response, and underwent reduced apoptosis in comparison with wild-type cells. A higher number of memory precursor effector cells and memory subsets was detectable in FoxO3a-deficient mice compared with wild-type mice. Furthermore, FoxO3a-deficient memory CD8(+) T cells upon transfer into normal or RAG1-deficient mice displayed enhanced survival. These results suggest that FoxO3a acts in a cell-intrinsic manner to regulate the survival of primed CD8(+) T cells.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Activación de Linfocitos
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Subgrupos Linfocitarios
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Linfocitos T CD8-positivos
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Factores de Transcripción Forkhead
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Memoria Inmunológica
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Listeriosis
Idioma:
En
Revista:
J Immunol
Año:
2013
Tipo del documento:
Article
País de afiliación:
Canadá