Immune promotion of central nervous system remyelination

Remyelination by oligodendrocytes is the normal response to injury of the central nervous system (CNS) following experimental demyelination by toxins and viruses in rodents. By contrast, in immune-mediated myelin disorders such as human multiple sclerosis (MS), Theiler's virus-induced demyelination, remyelination is incomplete. This chapter considers two hypotheses to explain why myelin repair is incomplete in these disorders. Hypothesis I is that myelin repair is the normal consequence of primary myelin injury but there are immune factors that prevent its full expression. Hypothesis II is that there are immune factors within some demyelinated lesions that when present, promote new myelin synthesis. To test hypothesis II, the chapter generates polyclonal immunoglobulins directed against normal CNS antigens. Transfer of immunoglobulins from mice immunized repeatedly with spinal cord homogenate resulted in 4–5-fold enhancement of remyelination in Theiler's virus infected mice. The chapter also generates a series of monoclonal antibodies directed against normal autoantigens that also promote CNS remyelination. These experiments support the concept that full CNS remyelination is possible in human demyelinating diseases such as MS.