diseases . 
1.3 Direct Gene Transfer and Modulation of the Immune 
System 
The utilization of catheter-based gene delivery in vivo 
provided a model system for the introduction of recombinant gene- 
specific sites in vivo. Early studies focused on the 
demonstration that specific reporter genes could be expressed in 
vivo (21,22). Subseguent studies were designed to determine 
whether specific biologic responses could be induced at sites of 
recombinant gene transfer. To address this question, a highly 
immunogenic molecule, a foreign major histocompatibility complex 
(MHC) , was used to elicit an immune response in the iliofemoral 
artery using a porcine model. The human HLA-B7 gene was 
introduced using direct gene transfer with a retroviral vector or 
DNA liposome complex (19) . With either delivery system, 
expression of the recombinant HLA-B7 gene product could be 
demonstrated at specific sites within the vessel wall. More 
importantly, the expression of this foreign histocompatibility 
antigen induced an immunologic response at the sites of genetic 
modification. This response included a granulomatous mononuclear 
cell infiltrate beginning 10 days after introduction of the 
recombinant -gene. This response resolved by 75 days after gene 
transfer; however, a specific cytolytic T cell response against 
the HLA-B7 molecule was persistent. This study demonstrated that 
a specific immunologic response could be induced by the 
introduction of a foreign recombinant gene at a specific site in 
vivo. Moreover, this provided one of the first indications that 
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