Transduction of a foreign histocompatibility gene into the arterial wall induces vasculitis.
Autoimmune vasculitis represents a disease characterized by focal inflammation within arteries at multiple sites in the vasculature. Therapeutic interventions in this disease are empirical and often unsuccessful, and the mechanisms of immune injury are not well-defined. The direct transfer of recombinant genes and their expression in the arterial wall provides an opportunity to explore the pathogenesis and treatment of vascular disease. In this report, an animal model for vasculitis has been developed. Inflammation has been elicited by direct gene transfer of a foreign class I major histocompatibility complex gene, HLA-B7, to specific sites in porcine arteries. Transfer and expression of this recombinant gene was confirmed by a polymerase chain reaction and immunohistochemistry, and cytolytic T cells specific for HLA-B7 were detected. These findings demonstrate that expression of a recombinant gene in the vessel wall can induce a focal immune response and suggest that vessel damage induced by cell-mediated immune injury can initiate vasculitis.
Nabel
E G
EG
Howard Hughes Medical Institute, University of Michigan Medical Center, Department of Internal Medicine, Ann Arbor 48109-0650.
Plautz
G
G
Nabel
G J
GJ
D000818:Animals; D001158:Arteries / Q000276:immunology*; D001483:Base Sequence; D003602:Cytotoxicity, Immunologic; D004730:Endothelium, Vascular / Q000276:immunology; D005805:Genes, MHC Class I; D005818:Genetic Engineering / Q000379:methods; D015793:HLA-B7 Antigen / Q000276:immunology*; D007111:Immunity, Cellular; D008081:Liposomes; D008969:Molecular Sequence Data; D013552:Swine; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D014162:Transfection; D014657:Vasculitis / Q000276:immunology* / Q000473:pathology
D015793:HLA-B7 Antigen; D008081:Liposomes