Aw Danielle, Hilliard Lucy, Nishikawa Yoshio, Cadman Emma T, Lawrence Rachel A, Palmer Donald B
Department of Comparative Biomedical Sciences, Royal Veterinary College, University of London, London, UK.
Immunology. 2016 May;148(1):92-101. doi: 10.1111/imm.12590. Epub 2016 Mar 17.
The precise mechanisms responsible for immunosenescence still remain to be determined, however, considering the evidence that disruption of the organization of primary and secondary lymphoid organs results in immunodeficiency, we propose that this could be involved in the decline of immune responses with age. Therefore, we investigated the integrity of the splenic microarchitecture in mice of increasing age and its reorganization following immune challenge in young and old mice. Several differences in the anatomy of the spleen with age in both the immune and stromal cells were observed. There is an age-related increase in the overall size of the white pulp, which occurs primarily within the T-cell zone and is mirrored by the enlargement of the T-cell stromal area, concurrent to the distinct boundary between T cells and B cells becoming less defined in older mice. In conjunction, there appears to be a loss of marginal zone macrophages, which is accompanied by an accumulation of fibroblasts in the spleens from older animals. Furthermore, whereas the reorganization of the white pulp is resolved after several days following antigenic challenge in young animals, it remains perturbed in older subjects. All these age-related changes within the spleen could potentially contribute to the age-dependent deficiencies in functional immunity.
免疫衰老的确切机制仍有待确定,然而,鉴于有证据表明初级和次级淋巴器官的组织结构破坏会导致免疫缺陷,我们认为这可能与免疫反应随年龄下降有关。因此,我们研究了不同年龄小鼠脾脏微结构的完整性,以及年轻和老年小鼠免疫挑战后脾脏的重组情况。在免疫细胞和基质细胞中均观察到脾脏解剖结构随年龄增长存在一些差异。白髓的总体积随年龄增加,主要发生在T细胞区,同时T细胞基质区域扩大,与之相伴的是老年小鼠中T细胞和B细胞之间的明显界限变得不那么清晰。与此同时,边缘区巨噬细胞似乎有所减少,老年动物脾脏中出现成纤维细胞积聚。此外,在年轻动物中,抗原刺激几天后白髓的重组得以解决,而在老年动物中仍处于紊乱状态。脾脏内所有这些与年龄相关的变化都可能导致功能性免疫方面的年龄依赖性缺陷。