TY - JOUR
T1 - Vaccination with autoantigen protects against aggregated β-amyloid and glutamate toxicity by controlling microglia
T2 - Effect of CD4+CD25+ T cells
AU - Avidan, Hila
AU - Kipnis, Jonathan
AU - Butovsky, Oleg
AU - Caspi, Rachel R.
AU - Schwartz, Michael
PY - 2004/12
Y1 - 2004/12
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - CNS injury
KW - Neuroprotection
KW - Protective autoimmunity
KW - T cell-based vaccination
UR - http://www.scopus.com/inward/record.url?scp=10944246635&partnerID=8YFLogxK
U2 - 10.1002/eji.200424883
DO - 10.1002/eji.200424883
M3 - Article
C2 - 15549735
AN - SCOPUS:10944246635
SN - 0014-2980
VL - 34
SP - 3434
EP - 3445
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 12
ER -