T-cell brain infiltration and immature antigen-presenting cells in transgenic models of Alzheimer’s disease-like cerebral amyloidosis

Feretti, MT; Merlini, M; Späni, C; Gericke, C; Schweizer, N; Enzmann, Gaby; Engelhardt, Britta; Kulic, L; Suter, T; Nitsch, RM (2016). T-cell brain infiltration and immature antigen-presenting cells in transgenic models of Alzheimer’s disease-like cerebral amyloidosis. Brain, behavior, and immunity, 54, pp. 211-225. Elsevier 10.1016/j.bbi.2016.02.009

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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 local- isation 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, pro- duced 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 anti- gen 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. 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Enzmann, Gaby and Engelhardt, Britta

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0889-1591

Publisher:

Elsevier

Language:

English

Submitter:

Ursula Zingg-Zünd

Date Deposited:

22 May 2017 11:50

Last Modified:

22 May 2017 11:57

Publisher DOI:

10.1016/j.bbi.2016.02.009

PubMed ID:

26872418

Uncontrolled Keywords:

Alzheimer’s disease; Amyloid-beta peptide; Interferon gamma; MHC-II; T-cell

BORIS DOI:

10.7892/boris.95357

URI:

https://boris.unibe.ch/id/eprint/95357

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