Vaccination with autoantigen protects against aggregated beta-amyloid and glutamate toxicity by controlling microglia: effect of CD4+CD25+ T cells.
Neurodegenerative diseases differ in etiology but are propagated similarly. We show that neuronal loss caused by intraocular injection of aggregated beta-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 beta-amyloid, reduced the ocular neuronal loss. In mouse hippocampal slices, microglia encountering activated T cells overcame the cytotoxicity of aggregated beta-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.
Avidan
Hila
H
Department of Neurobiology, The Weizmann Institute of Science, Rehovot, Israel.
Kipnis
Jonathan
J
Butovsky
Oleg
O
Caspi
Rachel R
RR
Schwartz
Michal
M
D016229:Amyloid beta-Peptides / Q000276:immunology* / Q000633:toxicity; D000818:Animals; D001324:Autoantigens / Q000276:immunology / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018698:Glutamic Acid / Q000276:immunology / Q000633:toxicity*; D007249:Inflammation / Q000276:immunology; D051379:Mice; D017628:Microglia / Q000276:immunology* / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000276:immunology; D014611:Vaccination
D016229:Amyloid beta-Peptides; D001324:Autoantigens; D015375:Receptors, Interleukin-2; D018698:Glutamic Acid