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

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