Department of Immunology, University of Connecticut School of Medicine, Farmington.
Center on Aging, University of Connecticut School of Medicine, Farmington.
J Gerontol A Biol Sci Med Sci. 2019 Oct 4;74(11):1734-1743. doi: 10.1093/gerona/glz029.
Aging negatively impacts immunity, resulting in inefficient responses to vaccinations and infections. Fibroblastic reticular cells (FRCs) are the major stromal cell subset in lymph nodes (LNs) and play an intricate role in the orchestration and control of adaptive immune responses. Although stromal cells have a major impact on immune responses, the impact of aging on LN stromal cells remains unclear. Quantitative analysis of LN stromal cells by flow cytometry revealed that there are no significant differences in the number of stromal cells in young and aged LN at steady state but after influenza infection aged FRCs have delayed expansion as a result of reduced proliferation. Aged LNs also produce reduced levels of homeostatic chemokines, which correlates with reduced homing of naive T cells. Image analysis reveals that young and aged T-cell zone FRCs have similar morphology at steady state and after infection. Furthermore, aged FRCs did not appear to be a contributing factor in the reduced proliferation of young T cells transferred into aged LNs after influenza infection. These results demonstrate that aging alters LN stromal cell response to challenge and these age-related changes may be an underlying contributor to impaired immune responses in the elderly people.
衰老会对免疫系统产生负面影响，导致对疫苗接种和感染的反应效率降低。纤维母细胞网状细胞（FRC）是淋巴结（LN）中主要的基质细胞亚群，在协调和控制适应性免疫反应中发挥着复杂的作用。尽管基质细胞对免疫反应有重大影响，但衰老对 LN 基质细胞的影响尚不清楚。通过流式细胞术对 LN 基质细胞进行定量分析表明，在稳态下，年轻和衰老的 LN 中的基质细胞数量没有显著差异，但在流感感染后，由于增殖减少，衰老的 FRC 扩张延迟。衰老的 LN 还产生较低水平的稳态趋化因子，这与幼稚 T 细胞归巢减少相关。图像分析显示，在稳态和感染后，年轻和衰老的 T 细胞区 FRC 的形态相似。此外，在流感感染后将年轻 T 细胞转移到衰老的 LN 中，衰老的 FRC 似乎不是导致年轻 T 细胞增殖减少的因素。这些结果表明，衰老改变了 LN 基质细胞对挑战的反应，这些与年龄相关的变化可能是老年人免疫反应受损的一个潜在原因。
