Cellular and molecular mechanisms of recovery of rats from experimental autoimmune encephalomyelitis

Multiple sclerosis is inflammatory, autoimmune disease of the central nervous system (CNS). The immune response directed towards cells and structures of CNS tissue causes demyelinization and neurodegeneration, thus inducing various neurological deficits in patients. In majority of patients multiple sclerosis takes relapsing-remitting or chronic progressive course. Experimental autoimmune encephalomyelitis (EAE) induced in DA rats is a model of multiple sclerosis and shares numerous immunopathogenic features with the human disease. Still, there is a major difference in the clinical course, as EAE in DA rats is acute monophasic disease. DA rats completely recover from EAE and are highly resistant to further attempts of the disease induction. The main goal of this project is to identify cell populations and molecular mechanisms responsible for the recovery of DA rats from EAE and their resistance to EAE re-induction. Consequently, the obtained knowledge should be useful for improvement of multiple sclerosis therapy. Potential immunoregulatory cell populations and molecules will be identified during the course of EAE. Functional properties of these cells will be determined, as well as their interaction with resident CNS cells. Cell depletion, cell transfer, inhibitors and stimulators will be used for identification of cells and molecules responsible for recovery and resistance in DA rats EAE.