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 naïve 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 naïve CD8⁺ T‐cell pool. Collectively, these findings provide new insights into the cellular immune insufficiencies that accompany human aging.

中文翻译：

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降低成年人的幼稚CD8（+）T细胞启动功效。

衰老与疫苗效力受损和对传染性和恶性疾病的敏感性增加有关。CD8 ⁺ T细胞是针对病原体和肿瘤的免疫反应的关键参与者。在衰老的小鼠中，逐渐消失的CD8 ⁺ T细胞区室被认为会损害从头免疫反应的诱导，但尚无人类实验证据。在这里，我们使用了基于加速树突状细胞共培养系统的原始体外测定法，对未分离的外周血单个核细胞进行了检测，以检测人类志愿者中CD8 ⁺ T细胞的启动效率。使用这种方法，我们报告说，老年人在数量和质量上一直受到损害对模型抗原特异的从头CD8 ⁺ T细胞反应。体外CD8 ⁺ T细胞启动能力降低还与体内较差的初次免疫反应性有关。这种免疫缺陷可能是由于固有的细胞缺陷和幼稚的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功能不足提供了新的见解。