High efficiency gene transfer is an efficient way of defining therapeutic targets: a functional genomics approach

• Published in: Annals of the rheumatic diseases 2001-11, Vol.60 (suppl 3), p.iii13-iii17
• Main Authors: Foxwell, B M J, Yoshimura, S, Bondeson, J, Brennan, F M, Feldmann, M
• Format: Article
• Language: English
• Subjects: Adenoviridae - genetics; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antigen Presentation; Applied cell therapy and gene therapy; Autoimmune diseases; Autoimmune Diseases - immunology; B7-1 Antigen - analysis; Biological and medical sciences; Cell Culture Techniques; Cytokines; Dendritic cells; Dendritic Cells - physiology; Disease; DNA-Binding Proteins - genetics; Efficiency; Flow Cytometry; gene transfer; Genes; Genetic Vectors - pharmacology; Genomics; Humans; I-kappa B Proteins; Lipopolysaccharides - pharmacology; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Lymphocytes; Medical sciences; NF-kappa B - antagonists & inhibitors; NF-kappa B - physiology; NF-KappaB Inhibitor alpha; Pathogenesis; Studies; T-Lymphocytes - physiology; therapeutic targets; Transfection - methods; Transfusions. Complications. Transfusion reactions. Cell and gene therapy
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/ard.60.90003.iii13

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. METHOD Highly efficient adenoviral infection of dendritic cells for the delivery of transgenes was obtained. These viral vectors were used to introduce IκBα into dendritic cells for the inhibition of NF-κB. This was used to investigate the role of NF-κB in dendritic cell function. RESULTS By blocking the NF-κB function a potent inhibition of the expression of costimulating molecules by dendritic cells with the concomitant loss of T cell stimulating function was demonstrated. CONCLUSION The use of adenoviral vectors may be a useful way of studying the role of genes in dendritic cell function.