Department of Neurology and Neurological Sciences, Stanford School of Medicine, California, United States.
Department of Neurology and Pathology, University of California San Francisco School of Medicine, California, United States.
ASN Neuro. 2021 Jan-Dec;13:17590914211018117. doi: 10.1177/17590914211018117.
One hallmark of human aging is increased brain inflammation represented by glial activation. With age, there is also diminished function of the adaptive immune system, and modest decreases in circulating B- and T-lymphocytes. Lymphocytes traffic through the human brain and reside there in small numbers, but it is unknown how this changes with age. Thus we investigated whether B- and T-lymphocyte numbers change with age in the normal human brain. We examined 16 human subjects in a pilot study and then 40 human subjects from a single brain bank, ranging in age from 44-96 years old, using rigorous criteria for defining neuropathological changes due to age alone. We immunostained post-mortem cortical tissue for B- and T-lymphocytes using antibodies to CD20 and CD3, respectively. We quantified cell density and made a qualitative assessment of cell location in cortical brain sections, and reviewed prior studies. We report that density and location of both B- and T-lymphocytes do not change with age in the normal human cortex. Solitary B-lymphocytes were found equally in intravascular, perivascular, and parenchymal locations, while T-lymphocytes appeared primarily in perivascular clusters. Thus, any change in number or location of lymphocytes in an aging brain may indicate disease rather than normal aging.
人类衰老的一个标志是神经胶质细胞激活导致的大脑炎症增加。随着年龄的增长，适应性免疫系统的功能也会减弱，循环中的 B 细胞和 T 细胞数量也会适度减少。淋巴细胞会在人体大脑中流动，并在其中少量存在，但目前尚不清楚这一过程随年龄如何变化。因此，我们研究了正常人类大脑中 B 细胞和 T 细胞的数量是否会随年龄增长而发生变化。我们在一项初步研究中检查了 16 名人类受试者，然后在一个大脑库中检查了 40 名人类受试者，这些受试者的年龄从 44 岁到 96 岁不等，我们使用严格的标准来定义仅因年龄而导致的神经病理学变化。我们使用针对 CD20 和 CD3 的抗体分别对死后皮质组织中的 B 细胞和 T 细胞进行免疫染色。我们量化了细胞密度，并对皮质脑切片中的细胞位置进行了定性评估，并回顾了之前的研究。我们报告称，在正常人类皮质中，B 细胞和 T 细胞的密度和位置均不会随年龄增长而发生变化。孤立的 B 细胞同样存在于血管内、血管周围和实质部位，而 T 细胞主要出现在血管周围簇中。因此，衰老大脑中淋巴细胞数量或位置的任何变化都可能表明存在疾病，而不是正常衰老。
