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T-cell brain infiltration and immature antigen-presenting cells in transgenic models of Alzheimer's disease-like cerebral amyloidosis.
- Source :
-
Brain, behavior, and immunity [Brain Behav Immun] 2016 May; Vol. 54, pp. 211-225. Date of Electronic Publication: 2016 Feb 09. - Publication Year :
- 2016
-
Abstract
- Cerebral beta-amyloidosis, one of the pathological hallmarks of Alzheimer's disease (AD), elicits a well-characterised, microglia-mediated local innate immune response. In contrast, it is not clear whether cells of the adaptive immune system, in particular T-cells, react to cerebral amyloidosis in AD. Even though parenchymal T-cells have been described in post-mortem brains of AD patients, it is not known whether infiltrating T-cells are specifically recruited to the extracellular deposits of beta-amyloid, and whether they are locally activated into proliferating, effector cells upon interaction with antigen-presenting cells (APCs). To address these issues we have analysed by confocal microscopy and flow-cytometry the localisation and activation status of both T-cells and APCs in transgenic (tg) mice models of AD-like cerebral amyloidosis. Increased numbers of infiltrating T-cells were found in amyloid-burdened brain regions of tg mice, with concomitant up-regulation of endothelial adhesion molecules ICAM-1 and VCAM-1, compared to non-tg littermates. The infiltrating T-cells in tg brains did not co-localise with amyloid plaques, produced less interferon-gamma than those in controls and did not proliferate locally. Bona-fide dendritic cells were virtually absent from the brain parenchyma of both non-tg and tg mice, and APCs from tg brains showed an immature phenotype, with accumulation of MHC-II in intracellular compartments. These results indicate that cerebral amyloidosis promotes T-cell infiltration but interferes with local antigen presentation and T-cell activation. The inability of the brain immune surveillance to orchestrate a protective immune response to amyloid-beta peptide might contribute to the accumulation of amyloid in the progression of the disease.<br /> (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Alzheimer Disease metabolism
Alzheimer Disease pathology
Amyloid beta-Peptides metabolism
Amyloid beta-Protein Precursor metabolism
Amyloidosis pathology
Animals
Antigen Presentation
Antigen-Presenting Cells immunology
Antigen-Presenting Cells metabolism
Brain metabolism
Cerebral Amyloid Angiopathy metabolism
Cerebral Amyloid Angiopathy pathology
Cytokines metabolism
Dendritic Cells metabolism
Disease Models, Animal
Humans
Mice
Mice, Transgenic
Microglia metabolism
Phenotype
Plaque, Amyloid
T-Lymphocytes metabolism
T-Lymphocytes pathology
Up-Regulation
Alzheimer Disease immunology
Cerebral Amyloid Angiopathy immunology
T-Lymphocytes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2139
- Volume :
- 54
- Database :
- MEDLINE
- Journal :
- Brain, behavior, and immunity
- Publication Type :
- Academic Journal
- Accession number :
- 26872418
- Full Text :
- https://doi.org/10.1016/j.bbi.2016.02.009