Accelerated CD8+ T-cell memory and prime-boost response after dendritic-cell vaccination
Accelerated CD8+ T-cell memory and prime-boost response after dendritic-cell vaccination
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DOI：
10.1038/nm1257
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发表时间：
2005-07-01
期刊：
影响因子：
82.9
通讯作者：
Harty, JT
中科院分区：
文献类型：
--
作者：
Badovinac, VP;Messingham, KAN;Harty, JT
将记忆性T细胞数量有效提升至保护水平通常需要免疫接种之间有相对较长的间隔。在生物防御和癌症免疫治疗中，缩短这一间隔可能至关重要，因为在这些情况下快速的保护反应是必不可少的。在此，我们表明用肽包被的树突状细胞（DCs）进行疫苗接种可在4 - 6天内产生具有记忆细胞表型和功能的CD8(+) T细胞。这些早期记忆性CD8(+) T细胞在受到各种加强免疫接种时会进行强烈的二次扩增，导致效应T细胞和记忆T细胞数量增加以及保护性免疫增强。共注射CpG寡脱氧核苷酸（一种有效的炎症诱导剂，不会改变DC抗原呈递的持续时间）可阻止野生型小鼠中记忆T细胞的快速产生，但在缺乏干扰素（IFN）-γ受体的小鼠中则不会。这些数据表明DC疫苗接种刺激了记忆T细胞加速产生的途径，并提示炎症事件，包括IFN -γ对反应性T细胞的作用，控制着记忆CD8(+) T细胞的发育速度。
Efficient boosting of memory T- cell numbers to protective levels generally requires a relatively long interval between immunizations. Decreasing this interval could be crucial in biodefense and cancer immunotherapy, in which rapid protective responses are essential. Here, we show that vaccination with peptide- coated dendritic cells (DCs) generated CD8(+) T cells with the phenotype and function of memory cells within 4 - 6 d. These early memory CD8(+) T cells underwent vigorous secondary expansion in response to a variety of booster immunizations, leading to elevated numbers of effector and memory T cells and enhanced protective immunity. Coinjection of CpG oligodeoxynucleotides, potent inducers of inflammation that did not alter the duration of DC antigen display, prevented the rapid generation of memory T cells in wild- type mice but not in mice lacking the interferon (IFN)-gamma receptor. These data show that DC vaccination stimulates a pathway of accelerated generation of memory T cells, and suggest that events of inflammation, including the action of IFN-gamma on the responding T cells, control the rate of development of memory CD8(+) T cells.