Differential tumor necrosis factor alpha expression by astrocytes from experimental allergic encephalomyelitis-susceptible and -resistant rat strains

A variety of animal models exist for the study of CNS disease involving inflammatory demyelinating lesions . The best characterized experimental model for CNS autoimmune disease is experimental allergic encephalomyelitis (EAE). This disease is induced by injection of myelin basic protein (MBP) or transfer of encephalitogenic MBP-specific T cells to naive recipients . EAE is characterized by invasion of the CNS by T lymphocytes and macrophages, demyelination, and acute, chronic, or chronic relapsing paralysis. The mediators of this disease are MBP-reactive T helper cells that are class II MHC restricted (see for review, reference 22 ) . It has been suggested that antigen-specific autoimmune T cells are responsible for initiation ofdisease, and that perpetuation ofdisease and subsequent demyelination may be the result ofan influx oflargely non-antigen-specific inflammatory cells of the recipient animal (23) . There appears to be genetic control of susceptibility to EAE . In inbred rat strains, Lewis rats (RT 11 haplotype) are susceptible to EAE, whereas Brown-Norway (BN) rats (RT1°) are resistent . Lewis x BN Fl rats have disease severity one-tenth that of Lewis rats. Disease susceptibility appears to be linked to MHC alleles, although non-MHC genes may play a small role in contributing to EAE (24) (25) (26) .