UNIMPAIRED AUTOREACTIVE T-CELL TRAFFIC WITHIN THE CENTRAL-NERVOUS-SYSTEM DURING TUMOR-NECROSIS-FACTOR RECEPTOR-MEDIATED INHIBITION OF EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS

The critical role of tumor necrosis factor (TNF) as a mediator in auto immune inflammatory processes is evident from in vivo studies with TNF -blocking agents, However, the mechanisms by which TNF, and possibly a lso its homologue lymphotoxin alpha, contributes to development of pat hology in rheumatoid arthritis and Crohn disease and in animal models like experimental autoimmune encephalomyelitis is unclear, Possibiliti es include regulation of vascular adhesion molecules enabling leukocyt e movement into tissues or direct cytokine-mediated effector functions such as mediation of tissue damage, Here we shelf that administration of a TNF receptor (55 kDa)-IgG fusion protein prevented clinical sign s of actively induced experimental autoimmune encephalomyelitis. Signi ficantly, the total number of CD4(+=)T lymphocytes isolated from the c entral nervous system of clinically healthy treated versus diseased co ntrol animals was comparable, By using a CD45 congenic model of passiv ely transferred experimental autoimmune encephalomyelitis to enable tr acking of myelin basic protein-specific effector T lymphocytes, preven tion of clinical signs of disease was again demonstrated in treated an imals but without quantitative or qualitative impediment to the moveme nt of autoreactive T lymphocytes to and within the central nervous sys tem, Thus, despite the uninterrupted movement of specific T lymphocyte s into the target tissue, subsequent disease development was blocked, This provides compelling evidence for a direct effector role of TNF/ly mphotoxin alpha in autoimmune tissue damage.