Effective antigen presentation by dendritic cells is NF-[kappa]B dependent: coordinate regulation of MHC, co-stimulatory molecules and cytokines

• Published in: International immunology 2001-05, Vol.13 (5), p.675
• Main Authors: Yoshimura, Satomichi, Bondeson, Jan, Foxwell, Brian M J, Brennan, Fionula M, Feldmann, Marc
• Format: Article
• Language: English
• ISSN: 0953-8178; 1460-2377

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-[kappa]B, I[kappa]B[alpha], we show that DC antigen presentation is NF-[kappa]B dependent. The mechanism for this is that NF-[kappa]B is essential for three aspects of antigen-presenting function: blocking NF-[kappa]B 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 I[kappa]B[alpha], indicating that NF-[kappa]B also regulates the duration of T cell-DC interaction. These results establish NF-[kappa]B 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.