A CRITICAL ROLE FOR LYMPHOTOXIN IN EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS

The lymphotoxin (LT)/tumor necrosis factor (TNF) family has been impli cated in the neurologic inflammatory diseases multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE). To determine the ro le of individual family members in EAE, C57BL/6 mice, LT-alpha-deficie nt (LT-alpha(-/-) mice), or LT-beta-deficient (LT-beta(-/-) mice), and their wild-type (WT) littermates were immunized with rat myelin oligo dendrocyte glycoprotein (MOG) peptide 35-55. C57BL/6 and WT mice devel oped chronic, sustained paralytic disease with average maximum clinica l scores of 3.5 and disease indices (a measure of day of onset and sus tained disease scores) ranging from 367 to 663 with central nervous sy stem (CNS) inflammation and demyelination. LT-beta(-/-) mice were prim ed so that their splenic lymphocytes proliferated in response to MOG 3 5-55 and the mice produced anti-MOG antibody. However, LT-alpha(-/-) m ice were quite resistant to EAE with low average clinical scores (<1), an average disease index of 61, and the neglible CNS inflammation and demyelination. WT T cells transferred EAE to LT-alpha(-/-) recipients . LT-beta(-/-) mice were susceptible to EAE, though less than WT, with an average maximum clinical score of 1.9 and disease index of 312. Th ese data implicate T cell production of LT-a! in MOG EAE and support a major role for LT-alpha 3, a minor role for the LT-alpha/beta complex , and by inference, no role for TNF-alpha.