| First Author | Browne TC | Year | 2013 |
| Journal | J Immunol | Volume | 190 |
| Issue | 5 | Pages | 2241-51 |
| PubMed ID | 23365075 | Mgi Jnum | J:193461 |
| Mgi Id | MGI:5468585 | Doi | 10.4049/jimmunol.1200947 |
| Citation | Browne TC, et al. (2013) IFN-gamma Production by Amyloid beta-Specific Th1 Cells Promotes Microglial Activation and Increases Plaque Burden in a Mouse Model of Alzheimer's Disease. J Immunol 190(5):2241-51 |
| abstractText | Alzheimer's disease (AD) is characterized by the presence of amyloid-beta (Abeta)-containing plaques, neurofibrillary tangles, and neuronal loss in the brain. Inflammatory changes, typified by activated microglia, particularly adjacent to Abeta 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 Abeta-specific T cells on Abeta 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-gamma or IL-17. Abeta-specific CD4 T cells generated by immunization with Abeta 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 Abeta 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-gamma Ab. Our study suggests that release of IFN-gamma from infiltrating Th1 cells significantly accelerates markers of diseases in an animal model of AD. |
