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 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-alpha, but not IFN-gamma, 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.
Wildbaum
G
G
Department of Immunology, and. Rappaport Family Institute for Research in the Medical Sciences and Department of Morphological Sciences, Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel.
Westermann
J
J
Maor
G
G
Karin
N
N
D000818:Animals; D017209:Apoptosis; D001323:Autoantibodies / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000628:therapy; D053222:Fas Ligand Protein; D005260:Female; D007113:Immunity, Innate; D007156:Immunologic Memory; D007167:Immunotherapy; D007371:Interferon-gamma / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000627:therapeutic use; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D019444:Vaccines, DNA / Q000276:immunology* / Q000627:therapeutic use
D001323:Autoantibodies; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D019444:Vaccines, DNA; D007371:Interferon-gamma