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

Hila Avidan, Jonathan Kipnis, Oleg Butovsky, Rachel R. Caspi, Michael Schwartz

Research output: Contribution to journalArticle

57 Scopus citations

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.

Original languageEnglish
Pages (from-to)3434-3445
Number of pages12
JournalEuropean Journal of Immunology
Volume34
Issue number12
DOIs
StatePublished - Dec 2004
Externally publishedYes

Keywords

  • Alzheimer's disease
  • CNS injury
  • Neuroprotection
  • Protective autoimmunity
  • T cell-based vaccination

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