Roles of TNF-related apoptosis-inducing ligand in experimental autoimmune encephalomyelitis

TRAIL, the TNF-related apoptosis-inducing ligand, induces apoptosis of tumo r cells, but not normal cells; the roles of TRAIL in nontransformed tissues are unknown. Using a soluble TRAIL receptor, we examined the consequences of TRAIL blockade in an animal model of multiple sclerosis. We found that c hronic TRAIL blockade in mice exacerbated experimental autoimmune encephalo myelitis induced by myelin oligodendrocyte glycoprotein. The exacerbation w as evidenced primarily by increases in disease score and degree of inflamma tion in the CNS. Interestingly, the degree of apoptosis of inflammatory cel ls In the CNS was not affected by TRAIL blockade, suggesting that TRAIL may not regulate apoptosis of inflammatory cells in experimental autoimmune en cephalomyelitis. By contrast, myelin oligodendrocyte glycoprotein-specific Th1 and Th2 cell responses were significantly enhanced in animals treated w ith the soluble TRAIL receptor. Based on these observations, we conclude th at unlike TNF, which promotes autoimmune inflammation, TRAIL inhibits autoi mmune encephalomyelitis and prevents activation of autoreactive T cells.