Cutting edge: FADD is not required for antigen receptor-mediated NF-kappaB activation.
J Immunol
; 175(12): 7800-4, 2005 Dec 15.
Article
en En
| MEDLINE
| ID: mdl-16339514
ABSTRACT
Recently, it has been demonstrated that stimulated T cells bearing defects in caspase-8 fail to promote nuclear shuttling of NF-kappaB complexes. Such cells display strikingly similar proliferative and survival defects as T cells lacking Fas-associated death domain protein (FADD) function. We characterized NF-kappaB signaling in T cells bearing a dominant-negative FADD transgene (FADDdd). Whereas FADDdd T cells displayed proliferative defects following activation, these were not a consequence of aberrant NF-kappaB signaling, as measured by IKK/IkappaB phosphorylation and IkappaB degradation. There were no appreciable defects in nuclear translocation of p65/Rel using ImageStream, a flow-based imaging cytometer. Pretreatment with benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone, a potent caspase inhibitor, also failed to impede canonical NF-kappaB signaling. Secretion of IL-2 and up-regulation of various activation markers occurred normally. Thus, FADD does not play an essential role in NF-kappaB activation, suggesting an alternative route by which this adaptor promotes the clonal expansion of T cells.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Receptores de Antígenos de Linfocitos T
/
Proteínas Adaptadoras Transductoras de Señales
/
Factor de Transcripción ReIA
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Immunol
Año:
2005
Tipo del documento:
Article
País de afiliación:
Estados Unidos