AN ANTIBODY TO LYMPHOTOXIN AND TUMOR-NECROSIS-FACTOR PREVENTS TRANSFER OF EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS

Uncertainty regarding pathogenic mechanisms has been a major impediment to effective prevention and treatment for human neurologic diseases such as multiple sclerosis, tropical spastic paraparesis, and AIDS demyelinating disease. Here, we implicate lymphotoxin (LT) (tumor necrosis factor β [TNF-β]) and TNF-α in experimental allergic encephalomyelitis (EAE), a murine model of an autoimmune demyelinating disease. In this communication, we report that treatment of recipient mice with an antibody that neutralizes LT and TNF-α prevents transfer of clone-mediated EAE. LNC-8, a myelin basic protein-specific T cell line, produces high levels of LT and TNF-α after activation by concanavalin A, antibody to the CD-3e component of the T cell receptor, or myelin basic protein presented in the context of syngeneic spleen cells. LNC-8 cells transfer clinical signs of EAE. When LNC-8 recipient mice were also treated with TN3.19.12, a monoclonal antibody that neutralizes LT and TNF-α, the severity of the transferred EAE was reduced, while control antibodies did not alter the disease. The effect of anti-LT/TNF-α treatment was long lived and has been sustained for 5 mo. These findings suggest that LT and TNF-α and the T cells that produce them play an important role in EAE. © 1990, Rockefeller University Press., All rights reserved.