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.
J Alzheimers Dis. 2011;27(1):99-111. doi: 10.3233/JAD-2011-102034.
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.
脑内淀粉样蛋白-β（Aβ）的积累是阿尔茨海默病（AD）的标志之一。人们已经观察到 T 细胞进入载有 Aβ 的血管和脑实质区域，其具有有益和有害的影响。使用一种新的 AD 小鼠模型，我们研究了允许 CD4 T 细胞特异性靶向载有 Aβ的脑区的分子机制。我们观察到，在 Aβ免疫接种后，CD11c+树突状细胞（DC）和 CD4 T 细胞主要存在于沉积有 Aβ的脑血管的血管周围和软脑膜空间中。CD11c+细胞表达高水平的 DC 成熟标志物 DEC-205、MHC 类 II 和 CD86。值得注意的是，大多数脑血管都与 Aβ斑块相邻，表达高水平的 ICAM-1 和 VCAM-1 粘附分子。我们提出，Aβ向软脑膜和血管周围空间的引流及其在那里的沉积为 DC 提供了抗原来源，以刺激其在向脑组织内的淀粉样斑块迁移的过程中产生 Aβ特异性 T 细胞。
