EXPRESSION OF BACTERIAL SUPERANTIGEN GENES IN MICE INDUCES LOCALIZED MONONUCLEAR CELL INFLAMMATORY RESPONSES

Bacterial superantigens are potent T cell activators, and superantigen proteins have been injected into mice and other animals to study T ce ll responses in vivo. When superantigen proteins are injected, however , the T cell stimulatory effects cannot be confined to specific tissue s. Therefore, to target superantigen expression to specific tissues, w e used gene transfer techniques to express bacterial superantigen gene s in mammalian cells in vitro and in tissues in vivo. Murine, human, a nd canine cells transfected with superantigen genes in vitro all produ ced superantigen proteins both intracellularly and extracellularly, as assessed by bioassay, immunocytochemistry, and antigen ELISA. Superan tigens produced by transfected eukaryotic cells retained their biologi c specificity for T cell receptor binding. Intramuscular injection of superantigen plasmid DNA in vivo induced an intense intramuscular mono nuclear cell infiltrate, an effect that could not be reproduced by int ramuscular injection of superantigen protein, Intradermal and intraven ous injection of superantigen DNA induced cutaneous and intrapulmonary mononuclear cell inflammatory responses, respectively, Thus, superant igen genes can be expressed by mammalian cells in vivo. Superantigen g ene therapy represents a novel method of targeting localized T cell in flammatory reactions, with potential application to treatment of cance r and certain infectious diseases.