Department of Immunology, Mayo Clinic College of Medicine and Science, Rochester, MN, United States.
Department of Medicine, Division of Rheumatology, Mayo Clinic College of Medicine and Science, Rochester, MN, United States.
Front Immunol. 2023 Aug 18;14:1250916. doi: 10.3389/fimmu.2023.1250916. eCollection 2023.
Immune memory is a requisite and remarkable property of the immune system and is the biological foundation of the success of vaccinations in reducing morbidity from infectious diseases. Some vaccines and infections induce long-lasting protection, but immunity to other vaccines and particularly in older adults rarely persists over long time periods. Failed induction of an immune response and accelerated waning of immune memory both contribute to the immuno-compromised state of the older population. Here we review how T cell memory is influenced by age. T cell memory is maintained by a dynamic population of T cells that are heterogeneous in their kinetic parameters under homeostatic condition and their function. Durability of T cell memory can be influenced not only by the loss of a clonal progeny, but also by broader changes in the composition of functional states and transition of T cells to a dysfunctional state. Genome-wide single cell studies on total T cells have started to provide insights on the influence of age on cell heterogeneity over time. The most striking findings were a trend to progressive effector differentiation and the activation of pro-inflammatory pathways, including the emergence of CD4 and CD8 cytotoxic subsets. Genome-wide data on antigen-specific memory T cells are currently limited but can be expected to provide insights on how changes in T cell subset heterogeneity and transcriptome relate to durability of immune protection.
免疫记忆是免疫系统的一个必要且显著的特性，也是疫苗成功降低传染病发病率的生物学基础。一些疫苗和感染会诱导持久的保护，但其他疫苗的免疫，特别是在老年人中，很少能长时间持续。免疫反应的诱导失败和免疫记忆的加速衰减都导致了老年人群的免疫功能受损状态。在这里，我们回顾了 T 细胞记忆如何受年龄影响。T 细胞记忆是由一群动态的 T 细胞维持的，这些 T 细胞在稳态下的动力学参数及其功能上存在异质性。T 细胞记忆的持久性不仅受到克隆后代的丧失的影响，还受到功能状态组成的更广泛变化和 T 细胞向功能失调状态的转变的影响。对总 T 细胞进行的全基因组单细胞研究开始提供关于年龄随时间推移对细胞异质性影响的见解。最引人注目的发现是效应分化的趋势逐渐增强，以及促炎途径的激活，包括 CD4 和 CD8 细胞毒性亚群的出现。关于抗原特异性记忆 T 细胞的全基因组数据目前有限，但有望提供关于 T 细胞亚群异质性和转录组的变化与免疫保护持久性的关系的见解。
