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

• DOI: 10.1016/j.bbi.2016.02.009
• Publication Date: 2016-02-09T12:42:59Z
• Authors: M.T. Ferretti; M. Merlini; C. Späni; C. Gericke; N. Schweizer; G. Enzmann; B. Engelhardt; L. Kulic; T. Suter; R.M. Nitsch
• Keywords: 0301 basic medicine; T-Lymphocytes; Immunology; Antigen-Presenting Cells; 610 Medicine & health; Mice, Transgenic; Plaque, Amyloid; Behavioral Neuroscience; Amyloid beta-Protein Precursor; Mice; 03 medical and health sciences; T-cell; Alzheimer Disease; 2802 Behavioral Neuroscience; Animals; Humans; MHC-II; Interferon gamma; 2403 Immunology; Antigen Presentation; 0303 health sciences; Amyloid beta-Peptides; Endocrine and Autonomic Systems; Brain; 11359 Institute for Regenerative Medicine (IREM); Amyloidosis; Dendritic Cells; Up-Regulation; 3. Good health; 2807 Endocrine and Autonomic Systems; Cerebral Amyloid Angiopathy; Disease Models, Animal; Phenotype; Cytokines; Microglia; Amyloid-beta peptide; Alzheimer’s disease

Cerebral beta-amyloidosis, one of the pathological hallmarks Alzheimer's disease (AD), elicits a well-characterised, microglia-mediated local innate immune response. In contrast, it is not clear whether cells adaptive system, in particular T-cells, react to cerebral amyloidosis AD. Even though parenchymal T-cells have been described post-mortem brains AD patients, known infiltrating are specifically recruited extracellular deposits beta-amyloid, and they locally activated into proliferating, effector upon interaction with antigen-presenting (APCs). To address these issues we analysed by confocal microscopy flow-cytometry localisation activation status both APCs transgenic (tg) mice models AD-like amyloidosis. Increased numbers were found amyloid-burdened brain regions tg mice, concomitant up-regulation endothelial adhesion molecules ICAM-1 VCAM-1, compared non-tg littermates. The did co-localise amyloid plaques, produced less interferon-gamma than those controls proliferate locally. Bona-fide dendritic virtually absent from parenchyma showed an immature phenotype, accumulation MHC-II intracellular compartments. These results indicate that promotes T-cell infiltration but interferes antigen presentation activation. inability surveillance orchestrate protective response amyloid-beta peptide might contribute progression disease.