Transgenic expression of the coxsackie/adenovirus receptor enables adenoviral-mediated gene delivery in naïve T cells
AUTOR(ES)
Wan, Yisong Y.
FONTE
The National Academy of Sciences
RESUMO
The inability to easily and efficiently introduce genes into primary T cells has hampered the investigation of the pathways controlling T cell fate. To enable adenoviral-mediated gene transfer into normal naïve T cells, transgenic (Tg) mice expressing the coxsackie/adenovirus receptor (CAR) in their T cell compartment were constructed. Whereas naïve T cells are resistant to adenoviral infection, Tg expression of CAR on T cells greatly facilitates adenoviral-mediated gene expression ex vivo, in vivo, and in differentiated T helper cells. Thus we have developed a technology for efficient gene delivery to naïve T cells. By using adenoviral vectors encoding specific inhibitors, we show that G1 cyclin-dependent kinase, NF-κB, and caspase activities are required for the proliferation of primary T cells. In addition, by expressing Bcl-xL protein at a level that closely approximates mitogen-induced levels, we demonstrate that Bcl-xL expression is sufficient to account for mitogen-mediated survival of primary T cells. Thus, adenoviral-mediated gene delivery to CAR Tg T cells should be useful for the analysis of many genes controlling T cell fate.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=17653Documentos Relacionados
- Efficient adenovirus-mediated gene transfer into primary T cells and thymocytes in a new coxsackie/adenovirus receptor transgenic model
- Adenoviral-mediated gene transfer in lymphocytes
- Enhancement of cardiac function after adenoviral-mediated in vivo intracoronary β2-adrenergic receptor gene delivery
- Adenoviral-mediated gene transfer to rabbit synovium in vivo.
- Adenoviral-mediated expression of Pcsk9 in mice results in a low-density lipoprotein receptor knockout phenotype