DNA vaccines encoding self antigens can suppress the incidence of experimental autoimmune encephalomyelitis (EAE), the animal disease model for multiple sclerosis. Recent DNA vaccine studies have used either skin or muscle as their routes of immunization. However, in EAE, an organ-specific disease, localization of DNA vaccine-induced immune responses within the central nervous system (CNS) may be a more practical application. In order to maximize long term effectiveness of encoded antigen synthesis and presentation in the CNS, we will target specific cell types that either circulate in the periphery or reside within the CNS. After ex vivo vaccination with a DNA minigene encoding the enecphalitogenic peptide PLP 139-151, transfected cell types will be transplanted into naive SJL/J mice. We will then induce EAE to determine whether ex vivo DNA vaccination can suppress the pathogenic potential of effector T cells in experimental mice. This study will maximize the delivery feature of DNA vaccination as treatment for organ-specific autoimmune diseases.