High efficiency gene transfer is an efficient way of defining therapeutic targets: a functional genomics approach.
BACKGROUND
Dendritic cells are the most potent antigen presenting cells and key to many aspects of the immune function. Studying the intracellular signalling mechanism used by dendritic cells would provide an insight into the functioning of these cells and give clues to strategies for immunomodulation.


METHODS
Highly efficient adenoviral infection of dendritic cells for the delivery of transgenes was obtained. These viral vectors were used to introduce IkappaB alpha into dendritic cells for the inhibition of NF-kappaB. This was used to investigate the role of NF-kappaB in dendritic cell function.


RESULTS
By blocking the NF-kappaB function a potent inhibition of the expression of costimulating molecules by dendritic cells with the concomitant loss of T cell stimulating function was demonstrated.


CONCLUSIONS
The use of adenoviral vectors may be a useful way of studying the role of genes in dendritic cell function.
Foxwell
B M
BM
Kennedy Institute of Rheumatology Division, Imperial College School of Medicine, London, UK. b.foxwell@ic.ac.uk
Yoshimura
S
S
Bondeson
J
J
Brennan
F M
FM
Feldmann
M
M
D000256:Adenoviridae / Q000235:genetics; D017951:Antigen Presentation; D001327:Autoimmune Diseases / Q000276:immunology*; D018122:B7-1 Antigen / Q000032:analysis; D018929:Cell Culture Techniques; D004268:DNA-Binding Proteins / Q000235:genetics; D003713:Dendritic Cells / Q000502:physiology*; D005434:Flow Cytometry; D005822:Genetic Vectors / Q000494:pharmacology; D006801:Humans; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology; D014162:Transfection / Q000379:methods
D018122:B7-1 Antigen; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha