title: Dendritic cells regulate amyloid-β-specific T-cell entry into the brain: the role of perivascular amyloid-β.
abstract: Amyloid-β (Aβ) accumulation in the brain is one of the hallmarks of Alzheimer's disease (AD). T-cell entry into vascular and parenchymal brain areas loaded with Aβ has been observed with both beneficial as well as detrimental effects. Using a new AD mouse model, we studied the molecular mechanisms allowing CD4 T cells to specifically target Aβ-loaded brain areas. We observed that following Aβ immunization, CD11c+ dendritic cells (DCs) and CD4 T cells occurred primarily in the perivascular and leptomeningial spaces of cerebral vessels deposited with Aβ. CD11c+ cells expressed high levels of the DC maturation markers DEC-205, MHC class II and CD86. Notably, the majority of cerebral blood vessels were found adjacent to Aβ plaques, expressing high levels of the ICAM-1 and VCAM-1 adhesion molecules. We propose that the drainage of Aβ to the leptomeningeal and perivascular spaces and its deposition there provide the antigenic source for DCs to stimulate Aβ-specific T cells on their way to target amyloid plaques within the brain tissue.
authors.affiliation: The Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences, and The National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Yair
authors.initials: Y
authors.lastname: Fisher
authors.forename: Anna
authors.initials: A
authors.lastname: Nemirovsky
authors.forename: Rona
authors.initials: R
authors.lastname: Baron
authors.forename: Alon
authors.initials: A
authors.lastname: Monsonego
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D001808:Blood Vessels / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000276:immunology / Q000378:metabolism*; D039521:CD11c Antigen / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D003713:Dendritic Cells / Q000276:immunology / Q000502:physiology*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000473:pathology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics; D037181:Lectins, C-Type / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015778:Minor Histocompatibility Antigens; D018991:Myelin Proteolipid Protein / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D015703:Antigens, CD; D051940:B7-2 Antigen; D039521:CD11c Antigen; C093569:DEC-205 receptor; D000949:Histocompatibility Antigens Class II; D037181:Lectins, C-Type; D015778:Minor Histocompatibility Antigens; D018991:Myelin Proteolipid Protein; D011956:Receptors, Cell Surface; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma