Vaccination with autoantigen protects against aggregated β‐amyloid and glutamate toxicity by controlling microglia: effect of CD4+CD25+ T cells

Publisher Website
Google Scholar
Abstract
Neurodegenerative diseases differ in etiology but are propagated similarly. We show that neuronal loss caused by intraocular injection of aggregated β‐amyloid was significantly greater in immunodeficient mice than in normal mice. The neurodegeneration was attenuated or augmented by elimination or addition, respectively, of naturally occurring CD4+CD25+ regulatory T cells (Treg). Vaccination with retina‐derived antigens or with the synthetic copolymer glatiramer acetate (Copolymer‐1, Cop‐1), but not with β‐amyloid, reduced the ocular neuronal loss. In mouse hippocampal slices, microglia encountering activated T cells overcame the cytotoxicity of aggregated β‐amyloid. These findings support the concept of “protective autoimmunity”, show that a given T cell‐based vaccination is protective at a particular site irrespective of toxicity type, and suggest that locally activated T cells induce a microglial phenotype that helps neurons withstand the insult. Alzheimer's and other neurodegenerative diseases might be arrested or retarded by vaccination with Cop‐1 or related compounds or by treatment with compounds that weaken Treg suppression.