An Alternative Pathway of NF-κB Activation Results in Maturation and T Cell Priming Activity of Dendritic Cells Overexpressing a Mutated IκBα

• Published in: Journal of Immunology 2007-02, Vol.178 (3), p.1301-1311
• Main Authors: Moore, Fabrice, Buonocore, Sofia, Aksoy, Ezra, Ouled-Haddou, Najate, Goriely, Stanislas, Lazarova, Elena, Paulart, Frédéric, Heirman, Carlo, Vaeremans, Elsy, Thielemans, Kris, Goldman, Michel, Flamand, Véronique
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606; 1365-2567
• DOI: 10.4049/jimmunol.178.3.1301

Maturation of dendritic cells (DC) is a critical step in the induction of T cell responses and depends on the activation of NF-κB transcription factors. Therefore, inhibition of NF-κB activation has been proposed as a strategy to maintain DC in an immature stage and to promote immune tolerance. Herein, we generated murine myeloid DC expressing a mutated IκBα acting as a superrepressor of the classical NF-κB pathway (s-rIκB DC) to investigate the consequences of NF-κB inhibition on the ability of DC to prime T cell responses. Upon in vitro LPS activation, maturation of s-rIκB DC was profoundly impaired as indicated by defective up-regulation of MHC class II and costimulatory molecules and reduced secretion of IL-12 p70 and TNF-α. In contrast, after injection, s-rIκB DC had the same capacity as control DC to migrate to draining lymph node and to induce Th1- and Th2-type cytokine production in a MHC class II-incompatible host mice. Likewise, s-rIκB DC pulsed with OVA were as efficient as control DC to induce Ag-specific T cell responses in vivo. Indeed, further in vitro experiments established that s-rIκB DC undergo efficient maturation upon prolonged contact with activated T cells via the alternative pathway of NF-κB activation triggered at least partly by lymphotoxin β receptor ligation and involving processing of p100/RelB complexes.