SPONTANEOUS CNS REMYELINATION IN BETA(2) MICROGLOBULIN-DEFICIENT MICEFOLLOWING VIRUS-INDUCED DEMYELINATION

Animal models with selective genetic immunodeficiencies are useful too ls to identify pathogenic mechanisms of disease. Resistant (C57BL/6F 1 29/5) (H-2(b)) mice are rendered susceptible to Theiler's murine encep halomyelitis virus-induced demyelination by genetic disruption of the beta(2) microglobulin gene [beta(2)m(-/-)]. The absence of beta(2)m pr events the expression of major histocompatibility complex class I mole cules and normal levels of functional CD8(+) T cells. We tested whethe r genetic depletion of beta(2)m would permit CNS remyelination after c hronic demyelination induced by the Daniel's strain of Theiler's virus . In contrast to the minimal spontaneous remyelination observed in SJL /J mice after infection with the Daniel's strain of Theiler's virus, c hronically infected beta(2)m(-/-) mice showed extensive and progressiv e spontaneous CNS remyelination at 6, 12, and 18 months after infectio n. Spontaneous remyelination by both oligodendrocytes and Schwann cell s occurred despite the presence of persistent virus antigen and RNA, b ut was associated with diminished virus-specific humoral and delayed-t ype hypersensitivity responses. These experiments support the hypothes is that the immune response inhibits myelin regeneration after virus-i nduced CNS demyelination.