Epitopes described in "IFN-γ Production by amyloid β-specific Th1 cells promotes microglial activation and increases plaque burden in a mouse model of Alzheimer's disease."

Article Authors:Tara C Browne; Keith McQuillan; Róisín M McManus; Julie-Ann O'Reilly; Kingston H G Mills; Marina A Lynch
Article Title:IFN-γ Production by amyloid β-specific Th1 cells promotes microglial activation and increases plaque burden in a mouse model of Alzheimer's disease.
Reference Detail
Reference ID:1025707
Abstract:Alzheimer's disease (AD) is characterized by the presence of amyloid- (A)-containing plaques, neurofibrillary tangles, and neuronal loss in the brain. Inflammatory changes, typified by activated microglia, particularly adjacent to A 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 A-specific T cells on A 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- or IL-17. A-specific CD4 T cells generated by immunization with A 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 A 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- Ab. Our study suggests that release of IFN- from infiltrating Th1 cells significantly accelerates markers of diseases in an animal model of AD.
Affiliations:Trinity College Institute of Neuroscience, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
Reference Type:Literature
PubMed ID:23365075
Journal:J Immunol
Journal Volume:190
Article Pages:2241-51
Journal ISSN:1550-6606
Article Chemical List:Amyloid beta-Peptides;Amyloid beta-Protein Precursor;Antibodies;Interleukin-17;Presenilin-1;Interferon-gamma
Article MeSH List:Adoptive Transfer; Alzheimer Disease(immunology; pathology); Amyloid beta-Peptides(genetics; immunology); Amyloid beta-Protein Precursor(genetics; immunology); Animals; Antibodies(pharmacology); Brain(drug effects; immunology; pathology); Cell Movement(drug effects); Disease Models, Animal; Gene Expression; Interferon-gamma(antagonists & inhibitors; immunology; secretion); Interleukin-17(genetics; immunology); Mice; Mice, Transgenic; Microglia(drug effects; immunology; pathology); Plaque, Amyloid(immunology; pathology); Presenilin-1(genetics; immunology); Th1 Cells(immunology; pathology; transplantation); Th17 Cells(immunology; pathology; transplantation); Th2 Cells(immunology; pathology; transplantation)
Curation Last Updated:2015-07-30 20:47:16