Animal models.

Different models of experimental autoimmune encephalomyelitis (EAE) have been successfully applied to investigate and manifold aspects of the autoimmune pathogenesis of multiple sclerosis. Studies using myelin-specific T-cell lines that transfer EAE to naive recipient animals established that only activated lymphocytes are able to cross the endothelial blood-brain barrier and cause autoimmune disease within the local parenchyma. All encephalitogenic T cells are CD4+ Th1-type lymphocytes that recognize autoantigenic peptides in the context of MHC class II molecules. In the case of myelin basic protein (MBP) specific EAE in the Lewis rat, the T-cell response is directed against one strongly dominant peptide epitope. The encephalitogenic T cells preferentially use one particular set of T-cell receptor genes. Although MBP is a strong encephalitogen in many species, a number of other brain protein are now known to induce EAE. These include mainly myelin components (PLP, MAG, and MOG), but also, the astroglial S-100 beta protein. Encephalitogenic T cells produce only inflammatory changes in the central nervous system, without extensive primary demyelination. Destruction of myelin and oligodendrocytes in these models requires additional effector mechanisms such as auto-antibodies binding to myelin surface antigens such as the myelin-oligodendrocyte glycoprotein.