Gene Therapy advance online publication, 17 November 2011; Doi: 10.1038/gt.2011.187.
Sutherland, R.M., Londrigan, S.L., Brady, J.L., Azher, H., Carrington, E.M., Zhan, Y., Vega-Ramos, J., Villadangos, J.A. & Lew, A.M.
“Shutdown of immunological priming and presentation after in vivo administration of adenovirus.”
A virus used as a shuttle in gene therapy that impairs immune system function may lead to novel therapeutics
Despite the utility of adenovirus (ADV) in the development and testing of gene therapies and vaccines, it can hamper the response of the immune system, according to research led by Andrew Lew and Robyn Sutherland of the Walter and Eliza Hall Institute of Medical Research, Australia.
Sutherland and her colleagues tested the effect of ADV on mice injected with chicken ovalbumin (OVA) protein, which induces a potent immune response mediated by cytotoxic T lymphocytes (CTLs). They found that injection of ADV before — but not after — OVA significantly impaired the CTL response. The impaired immune response was not due to a reduction in the number of CTLs or dendritic cells.
CD8+ dendritc cells normally internalize microbes by a process called endocytosis, then display fragments of them on their surface so that an immune response can be initiated. The team revealed that ADV inhibits the uptake of fluorescent beads by CD8+ dendritic cells. This indicates that ADV impairs the immune response by preventing endocytosis and presentation of subsequently encountered antigens by CD8+ dendritic cells.
“Shutdown of the CTL response is desirable in some situations,” says Sutherland, “so identification of the molecular basis of this phenomenon may lead to novel immunosuppressive treatments and is the basis of our ongoing research.”