title: Transgenic expression of the coxsackie/adenovirus receptor enables adenoviral-mediated gene delivery in naive T cells.
abstract: 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 naive T cells, transgenic (Tg) mice expressing the coxsackie/adenovirus receptor (CAR) in their T cell compartment were constructed. Whereas naive 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 naive T cells. By using adenoviral vectors encoding specific inhibitors, we show that G1 cyclin-dependent kinase, NF-kappaB, and caspase activities are required for the proliferation of primary T cells. In addition, by expressing Bcl-x(L) protein at a level that closely approximates mitogen-induced levels, we demonstrate that Bcl-x(L) 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.
authors.affiliation: Departments of Biochemistry and Molecular Genetics and Pediatrics, and Microbiology, Program in Molecular Biology, University of Colorado Health Sciences Center, BRB802, 4200 East Ninth Avenue, Denver, CO 80262, USA.
authors.forename: Y Y
authors.initials: YY
authors.lastname: Wan
authors.forename: R P
authors.initials: RP
authors.lastname: Leon
authors.forename: R
authors.initials: R
authors.lastname: Marks
authors.forename: C M
authors.initials: CM
authors.lastname: Cham
authors.forename: J
authors.initials: J
authors.lastname: Schaack
authors.forename: T F
authors.initials: TF
authors.lastname: Gajewski
authors.forename: J
authors.initials: J
authors.lastname: DeGregori
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D002455:Cell Division; D004770:Enterovirus / Q000235:genetics*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D011991:Receptors, Virus / Q000235:genetics*; D011995:Recombination, Genetic; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D014161:Transduction, Genetic
chemical_list: D011991:Receptors, Virus