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

Author： Yoshimura S. Bondeson J. Foxwell B.M.J. Brennan F.M. Feldmann M.

Publisher： Oxford University Press

ISSN： 1460-2377

Source： International Immunology, Vol.13, Iss.5, 2001-05, pp. : 675-683

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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-B, IBα, we show that DC antigen presentation is NF-B dependent. The mechanism for this is that NF-B is essential for three aspects of antigen-presenting function: blocking NF-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-α. In contrast adhesion molecules are up-regulated after infection with the adenovirus transferring IBα, indicating that NF-B also regulates the duration of T cell–DC interaction. These results establish NF-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.