A targeted DNA vaccine encoding Fas ligand defines its dual role in the regulation of experimental autoimmune encephalomyelitis
Gizi Wildbaum, … , Gila Maor, Nathan Karin
Gizi Wildbaum, … , Gila Maor, Nathan Karin
Published September 1, 2000
Citation Information: J Clin Invest. 2000;106(5):671-679. https://doi.org/10.1172/JCI8759.
View: Text | PDF
Article

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

Abstract

This study used naked DNA vaccination to induce breakdown of tolerance to self and thus elicit immunological memory to native, membrane-bound Fas ligand (FasL). Upon induction of experimental autoimmune encephalomyelitis (EAE), this memory was turned on to provide protective immunity. FasL-specific autoantibodies isolated from protected animals differentially downregulated the in vitro production of TNF-α, but not IFN-γ, by cultured T cells. These autoantibodies were highly protective when they were administered to rats at the onset of EAE. In contrast, administration of these FasL-specific Ab’s to EAE rats after the peak of the acute phase of disease prevented spontaneous recovery from disease. This extended illness is partially explained by inhibition of mononuclear cell apoptosis at the target organ, which resulted in increased accumulation of T cells and macrophages at the site of inflammation. Hence, FasL exerts two distinct, stage-specific regulatory functions in the control of this T-cell mediated autoimmune disease of the central nervous system.

Authors

Gizi Wildbaum, Juergen Westermann, Gila Maor, Nathan Karin

×

Figure 5

Options: View larger image (or click on image) Download as PowerPoint
Administration of FasL-specific Ab’s during the early stage of disease c...
Administration of FasL-specific Ab’s during the early stage of disease confers resistance to EAE. (a) Lewis rats were immunized with p68-86/CFA to develop active EAE (day 0). At various time points (days 7, 9, 10, and 12) these rats were administered 100 μg/rat of purified FasL-specific Ab’s, obtained as described in the legend to Figure 3. Control rats were administered either IgG from rats that were vaccinated with pcDNA3 and then subjected to active induction of disease (Figure 1, day 13), or with IgG from naive Lewis rats. All rats were then monitored for clinical signs daily by an observer blind to the treatment protocol. Results are shown as mean clinical score of six rats per group ± SE. (b) Lewis rats were administered L68-86 to induce transferred EAE (day 0). On days 4 and 5 these rats were administered 100 μg/rat of each of the Ab’s described in a. All rats were monitored for clinical signs daily by an observer blind to the treatment protocol. Results are shown as mean clinical score of six rats per group ± SE.