Age-Related Decline in Primary CD8+ T Cell Responses Is Associated with the Development of Senescence in Virtual Memory CD8+ T Cells
Age-Related Decline in Primary CD8+ T Cell Responses Is Associated with the Development of Senescence in Virtual Memory CD8+ T Cells
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DOI：
10.1016/j.celrep.2018.05.057
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发表时间：
2018-06-19
期刊：
影响因子：
8.8
通讯作者：
La Gruta, Nicole L.
中科院分区：
文献类型：
--
作者：
Quinn, Kylie M.;Fox, Annette;La Gruta, Nicole L.
与年龄相关的初级CD8(+)T细胞反应减少，部分原因是直接作用于原始CD8(+)T细胞以减少固有功能，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-VM)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，我们展示了T-VM细胞在老年小鼠和人类中的低增殖能力，尽管在年轻个体中高度增殖，而传统的幼稚T细胞(T-N细胞)在老年小鼠和人类中都保持着增殖能力。在小鼠体内的过继转移实验表明，幼稚的CD8T细胞可以获得老年环境造成的增殖性缺陷，但年轻环境不能挽救与年龄相关的增殖性功能障碍。分子分析表明，衰老的T-VM细胞表现出与衰老一致的特征，这标志着在抗原性未成熟的T细胞群体中观察到了衰老。
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-vM ) cells, but their contribution to age-related functional decline is unclear. Here, we show that T-vm cells are poorly proliferative in aged mice and humans, despite being highly proliferative in young individuals, while conventional naive T cells (T-N 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-vm cells exhibit a profile consistent with senescence, marking an observation of senescence in an antigenically naive T cell population.