Generalized autoimmunity of the nervous system (GANS) induced by a recombinant protein composed of major pathogenic determinants of MBP, IRBP, and P2 protein: Suppression of inflammation by a monoclonal antibody against activated rat T line cells

We have developed a new model of generalized autoimmunity of the rat nervous system to study differential immunoregulation, barrier-function, and parenchymal inflammatory processes. We designed a multicomponent synthetic gene encoding major pathogenic determinants for Lewis rats of myelin basic protein (MBP), interphotoreceptor retinoid binding protein (IRBP), and P2 protein. Immunization with the recombinant protein induces a monophasic disease with inflammatory lesions in the eye, brain, spinal cord, and peripheral nerves. Rats recovered from GANS were tolerant against the induction of experimental autoimmune encephalomyelitis (EAE), neuritis (EAN), and uveoretinitis (EAU) by immunization with synthetic autoantigen-peptides/CFA. To demonstrate an application of GANS we have used a monoclonal antibody raised against encephalitogenic rat T lymphocytes. We show that this monoclonal antibody is suppressing not only inflammatory cell infiltration of brain and spinal cord, but as well of the eyes and the peripheral nervous system.