Effective antigen presentation by dendritic cells is NF-kappaB dependent: coordinate regulation of MHC, co-stimulatory molecules and cytokines.
Int Immunol
; 13(5): 675-83, 2001 May.
Article
en En
| MEDLINE
| ID: mdl-11312255
ABSTRACT
Antigen presentation is a key rate-limiting step in the immune response. Dendritic cells (DC) are the most potent antigen-presenting cells for naive T cells, due to their high expression of MHC and co-stimulatory molecules, but little is known about the biochemical pathways that regulate this function. We here demonstrate that monocyte-derived mature DC can be infected with adenovirus at high efficiency (>95%) and that this procedure can be used to dissect out which pathways are essential for inducing DC antigen presentation to naive T cells. Using adenoviral transfer of the endogenous inhibitor of NF-kappaB, IkappaBalpha, we show that DC antigen presentation is NF-kappaB dependent. The mechanism for this is that NF-kappaB is essential for three aspects of antigen-presenting function blocking NF-kappaB coordinately down-regulates HLA class II, co-stimulatory molecules like CD80, CD86 and CD40, and immuno-stimulatory cytokines like IL-12 and tumor necrosis factor-alpha. In contrast adhesion molecules are up-regulated after infection with the adenovirus transferring IkappaBalpha, indicating that NF-kappaB also regulates the duration of T cell-DC interaction. These results establish NF-kappaB as an effective target for blocking DC antigen presentation and inhibiting T cell-dependent immune responses, and this finding has potential implications for the development of therapeutic agents for use in allergy, autoimmunity and transplantation.
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Base de datos:
MEDLINE
Asunto principal:
Células Dendríticas
/
FN-kappa B
/
Presentación de Antígeno
/
Proteínas I-kappa B
Idioma:
En
Revista:
Int Immunol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2001
Tipo del documento:
Article