Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.
Department of Microbiology and Immunology, The Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia.
Cell Rep. 2018 Jun 19;23(12):3512-3524. doi: 10.1016/j.celrep.2018.05.057.
Age-associated decreases in primary CD8 T cell responses occur, in part, due to direct effects on naive CD8 T cells to reduce intrinsic functionality, but the precise nature of this defect remains undefined. Aging also causes accumulation of antigen-naive but semi-differentiated "virtual memory" (T) cells, but their contribution to age-related functional decline is unclear. Here, we show that T cells are poorly proliferative in aged mice and humans, despite being highly proliferative in young individuals, while conventional naive T cells (T cells) retain proliferative capacity in both aged mice and humans. Adoptive transfer experiments in mice illustrated that naive CD8 T cells can acquire a proliferative defect imposed by the aged environment but age-related proliferative dysfunction could not be rescued by a young environment. Molecular analyses demonstrate that aged T cells exhibit a profile consistent with senescence, marking an observation of senescence in an antigenically naive T cell population.
年龄相关的原发性 CD8 T 细胞反应的下降部分是由于对幼稚 CD8 T 细胞的直接作用，导致内在功能降低，但这种缺陷的确切性质仍未确定。衰老还会导致抗原幼稚但半分化的“虚拟记忆”（T）细胞的积累，但它们对与年龄相关的功能下降的贡献尚不清楚。在这里，我们表明，T 细胞在衰老的小鼠和人类中增殖能力差，尽管在年轻个体中增殖能力很强，而传统的幼稚 T 细胞（T 细胞）在衰老的小鼠和人类中均保持增殖能力。在小鼠中的过继转移实验表明，幼稚 CD8 T 细胞可以获得由衰老环境引起的增殖缺陷，但年轻环境并不能挽救与年龄相关的增殖功能障碍。分子分析表明，衰老的 T 细胞表现出与衰老一致的特征，这标志着在抗原幼稚的 T 细胞群体中观察到衰老。
