T Cell factor 1 represses CD8+ effector T cell formation and function.
J Immunol
; 193(11): 5480-7, 2014 Dec 01.
Article
en En
| MEDLINE
| ID: mdl-25355919
ABSTRACT
The Wnt-responsive transcription factor T cell factor 1 (Tcf1) is well known for its role in thymic T cell development and the formation of memory CD8(+) T cells. However, its role in the initial phases of CD8(+) T effector cell formation has remained unexplored. We report that high levels of Wnt signaling and Tcf1 are operational in naive and memory CD8(+) T cells, whereas Wnt signaling and Tcf1 were low in effector CD8(+) T cells. CD8(+) T cells deficient in Tcf1 produce IFN-γ more rapidly, coinciding with increased demethylation of the IFN-γ enhancer and higher expression of the transcription factors Tbet and Blimp1. Moreover, virus-specific Tcf1(-/-) CD8(+) T cells show accelerated expansion in acute infection, which is associated with increased IFN-γ and TNF production and lower viral load. Genetic complementation experiments with various Tcf1 isoforms indicate that Tcf1 dosage and protein stability are critical in suppressing IFN-γ production. Isoforms lacking the ß-catenin binding domain are equally effective in inhibiting CD8(+) effector T cell formation. Thus, Tcf1 functions as a repressor of CD8(+) effector T cell formation in a ß-catenin/Wnt-independent manner.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Interferón gamma
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Linfocitos T CD8-positivos
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Factor Nuclear 1-alfa del Hepatocito
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Coriomeningitis Linfocítica
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Virus de la Coriomeningitis Linfocítica
Límite:
Animals
Idioma:
En
Revista:
J Immunol
Año:
2014
Tipo del documento:
Article
País de afiliación:
Países Bajos