Reduced naive CD8+ T-cell priming efficacy in elderly adults
Reduced naive CD8+ T-cell priming efficacy in elderly adults
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DOI：
10.1111/acel.12384
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发表时间：
2016-02-01
期刊：
影响因子：
7.8
通讯作者：
Appay, Victor
中科院分区：
文献类型：
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作者：
Briceno, Olivia;Lissina, Anna;Appay, Victor
衰老与疫苗效力受损以及对传染病和恶性疾病的易感性增加有关。CD8（+）T细胞是针对病原体和肿瘤的免疫反应的关键参与者。在老年小鼠中，幼稚CD8（+）T细胞区室的减少被认为会损害从头免疫应答的诱导，但在人类中还没有实验证据。在这里，我们使用了一种基于加速树突状细胞共培养系统的原始体外试验，在未分级的外周血单核细胞中检测人类志愿者中CD8（+）T细胞的启动功效。使用这种方法，我们报告说，老年人不断安装定量和定性受损的从头CD8（+）T细胞反应的模式抗原。体外CD8（+）T细胞引发能力降低与体内初级免疫应答差进一步相关。这种免疫缺陷可能是由于内在的细胞缺陷和幼稚CD8（+）T细胞池的大小减少而引起的。总的来说，这些发现为伴随人类衰老的细胞免疫抑制提供了新的见解。
Aging is associated with impaired vaccine efficacy and increased susceptibility to infectious and malignant diseases. CD8(+) T-cells are key players in the immune response against pathogens and tumors. In aged mice, the dwindling naive CD8(+) T-cell compartment is thought to compromise the induction of de novo immune responses, but no experimental evidence is yet available in humans. Here, we used an original in vitro assay based on an accelerated dendritic cell coculture system in unfractioned peripheral blood mononuclear cells to examine CD8(+) T-cell priming efficacy in human volunteers. Using this approach, we report that old individuals consistently mount quantitatively and qualitatively impaired de novo CD8(+) T-cell responses specific for a model antigen. Reduced CD8(+) T-cell priming capacity in vitro was further associated with poor primary immune responsiveness in vivo. This immune deficit likely arises as a consequence of intrinsic cellular defects and a reduction in the size of the naive CD8(+) T-cell pool. Collectively, these findings provide new insights into the cellular immune insufficiencies that accompany human aging.