Shutdown of immunological priming and presentation after in vivo administration of adenovirus
RM Sutherland, SL Londrigan, JL Brady, H Azher, EM Carrington, Y Zhan, J Vega-Ramos, JA Villadangos, AM Lew
GENE THERAPY | NATURE PUBLISHING GROUP | Published : 2012
Adenoviral (Adv) vectors are widely used in both experimental and clinical trials for vaccination and gene therapy. Recombinant Adv can evoke potent innate immune responses and adaptive immune responses to encoded antigens. However, how Adv infection affects the response to subsequently encountered antigens is poorly understood. We show that intravenously administered replication defective (E1 and E3 deleted) Adv educes functional changes in dendritic cells (DC) resulting in impaired priming of cytotoxic T lymphocytes (CTL) more than 7 days after Adv treatment. Generalized DC activation was indicated by transient upregulation of CD86 and reduced endocytosis of fluorescent beads. It is known ..View full abstract
This work was supported by the National Health and Medical Research Council of Australia, Juvenile Diabetes Research Foundation and Diabetes Australia Research Trust. This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIIS. We are grateful to Nicole Ashman for technical assistance with mice.