Central nervous system-targeted expression of the complement inhibitor sCrry prevents experimental allergic encephalomyelitis

Although generally thought of as a T cell-driven autoimmune disease, recent studies in experimental allergic encephalomyelitis (EAE), the animal model of multiple sclerosis, suggest a significant role for innate immune mechan isms. To address the possibility that the complement system plays a central role in these diseases, we developed a transgenic mouse with astrocyte-tar geted production of a soluble inhibitor of complement activation, complemen t receptor-related protein y (sCrry), Here, we show that sCrry transgenic m ice are either fully protected against EAE or develop significantly delayed clinical signs. These results indicate that complement activation may have an essential role in the pathogenesis of the disease and that complement-m ediated events may occur early during the effector phase of EAE. Furthermor e, this work underscores the importance of humoral immunity in amplifying a T cell-initiated pathogenic process.