An Alternative Pathway of Nf-kappab Activation Results in Maturation and T Cell Priming Activity of Dendritic Cells Overexpressing a Mutated Ikappabalpha.
From: Institute for Medical Immunology, Université Libre de Bruxelles, Gosselies, Belgium.
Journal of immunology (Baltimore, Md. : 1950)
- Publish Date: Feb 2007
- ISSN: 0022-1767
- Volume: 178
- Issue: 3
- Pages: 1301-11
- Medium: Print
- Language: English
- Citation (JAMA): Moore Fabrice, Buonocore Sofia, Aksoy Ezra, et al. An Alternative Pathway of Nf-kappab Activation Results in Maturation and T Cell Priming Activity of Dendritic Cells Overexpressing a Mutated Ikappabalpha.. J. Immunol. Feb 2007;178:1301-11
Abstract
Maturation of dendritic cells (DC) is a critical step in the induction of T cell responses and depends on the activation of NF-kappaB transcription factors. Therefore, inhibition of NF-kappaB 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 IkappaBalpha acting as a superrepressor of the classical NF-kappaB pathway (s-rIkappaB DC) to investigate the consequences of NF-kappaB inhibition on the ability of DC to prime T cell responses. Upon in vitro LPS activation, maturation of s-rIkappaB 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-alpha. In contrast, after injection, s-rIkappaB 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-rIkappaB 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-rIkappaB DC undergo efficient maturation upon prolonged contact with activated T cells via the alternative pathway of NF-kappaB activation triggered at least partly by lymphotoxin beta receptor ligation and involving processing of p100/RelB complexes.
Mesh Headings (Keywords): Animals, Antigen Presentation, Cell Differentiation, Cells, Cultured, Cytokines, Dendritic Cells, Gene Expression Regulation, Histocompatibility Antigens Class II, I-kappa B Proteins, Lipopolysaccharides, Mice, Mutation, NF-kappa B, T-Lymphocytes
Check for Full Text / PubMed Unique Identifier (PMID): 17237376
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