A targeted DNA vaccine encoding Fas ligand defines its dual role in the regulation of experimental autoimmune encephalomyelitis

This study used naked DNA vaccination to induce breakdown of tolerance to s elf and thus elicit immunological memory to native, membrane-bound Fas liga nd (FasL). Upon induction of experimental autoimmune encephalomyelitis (EAE ), this memory was turned on to provide protective immunity. Fast-specific autoantibodies isolated from protected animals differentially downregulated the in vitro production of TNF-alpha, but not IFN-gamma, by cultured T cel ls. These autoantibodies were highly protective when they were administered to rats at the onset of EAE. In contrast, administration of these Fast-spe cific Ab's to EAE rats after the peak of the acute phase of disease prevent ed spontaneous recovery from disease. This extended illness is partially ex plained by inhibition of mononuclear cell apoptosis at the target organ, wh ich resulted in increased accumulation of T cells and macrophages at the si te of inflammation. Hence, Fast exerts two distinct, stage-specific regulat ory functions in the control of this T-cell mediated autoimmune disease of the central nervous system.