IFN-γ Production by amyloid ß-specific Th1 cells promotes microglial activation and increases plaque burden in a mouse model of Alzheimer's disease.
J Immunol
; 190(5): 2241-51, 2013 Mar 01.
Article
en En
| MEDLINE
| ID: mdl-23365075
ABSTRACT
Alzheimer's disease (AD) is characterized by the presence of amyloid-ß (Aß)-containing plaques, neurofibrillary tangles, and neuronal loss in the brain. Inflammatory changes, typified by activated microglia, particularly adjacent to Aß plaques, are also a characteristic of the disease, but it is unclear whether these contribute to the pathogenesis of AD or are a consequence of the progressive neurodegenerative processes. Furthermore, the factors that drive the inflammation and neurodegeneration remain poorly understood. CNS-infiltrating T cells play a pivotal role in the pathogenesis of multiple sclerosis, but their role in the progression of AD is still unclear. In this study, we examined the role of Aß-specific T cells on Aß accumulation in transgenic mice that overexpress amyloid precursor protein and presenilin 1 (APP/PS1). We found significant infiltration of T cells in the brains of APP/PS1 mice, and a proportion of these cells secreted IFN-γ or IL-17. Aß-specific CD4 T cells generated by immunization with Aß and a TLR agonist and polarized in vitro to Th1-, Th2-, or IL-17-producing CD4(+) T cells, were adoptively transferred to APP/PS1 mice at 6 to 7 mo of age. Assessment of animals 5 wk later revealed that Th1 cells, but not Th2 or IL-17-producing CD4(+) T cells, increased microglial activation and Aß deposition, and that these changes were associated with impaired cognitive function. The effects of Th1 cells were attenuated by treatment of the APP/PS1 mice with an anti-IFN-γ Ab. Our study suggests that release of IFN-γ from infiltrating Th1 cells significantly accelerates markers of diseases in an animal model of AD.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Encéfalo
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Péptidos beta-Amiloides
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Interferón gamma
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Microglía
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Células TH1
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Placa Amiloide
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Enfermedad de Alzheimer
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Immunol
Año:
2013
Tipo del documento:
Article
País de afiliación:
Irlanda