IκB kinase ß is required for activation of NF-κB and AP-1 in CD3/CD28-stimulated primary CD4(+) T cells.
J Immunol
; 188(6): 2545-55, 2012 Mar 15.
Article
em En
| MEDLINE
| ID: mdl-22331067
ABSTRACT
Engagement of the TCR and CD28 coreceptor by their respective ligands activates signal transduction cascades that ultimately lead to the activation of the transcription factors NFAT, AP-1, and NF-κB, which are required for the expression of cytokines and T cell clonal expansion. Previous studies have demonstrated that in mature T cells, activation of AP-1 and NF-κB is dependent on protein kinase C θ, suggesting the existence of a common signaling pathway. In this study, we show that in human primary CD4(+) T cells, exposure to the cell-permeable IKKß inhibitor PS-1145 or genetic ablation of IKKß abrogates cell proliferation and impairs the activation of NF-κB and AP-1 transcription factors in response to engagement of CD3 and CD28 coreceptor. In addition, we show that stimulation of T cells in the absence of IKKß activity promotes the time-dependent and cyclosporine-sensitive expression of negative regulators of T cell signaling leading to a hyporesponsive state of T cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ativação Linfocitária
/
Linfócitos T CD4-Positivos
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NF-kappa B
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Fator de Transcrição AP-1
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Quinase I-kappa B
Limite:
Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article