Badovinac Vladimir P, Messingham Kelly A N, Jabbari Ali, Haring Jodie S, Harty John T
Department of Microbiology, 3-512 Bowen Science Building, 51 Newton Road, University of Iowa, Iowa City, Iowa 52240, USA.
Nat Med. 2005 Jul;11(7):748-56. doi: 10.1038/nm1257. Epub 2005 Jun 12.
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.
将记忆性T细胞数量有效提升至具有保护作用的水平通常需要在免疫接种之间间隔相对较长的时间。缩短这一间隔在生物防御和癌症免疫治疗中可能至关重要,因为在这些领域中快速产生保护性反应至关重要。在此,我们表明用肽包被的树突状细胞(DC)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后经历了强烈的二次扩增,导致效应性T细胞和记忆性T细胞数量增加,并增强了保护性免疫。共注射CpG寡脱氧核苷酸(一种不改变DC抗原展示持续时间的强效炎症诱导剂)可阻止野生型小鼠中记忆性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疫苗接种刺激了一条加速记忆性T细胞产生的途径,并表明包括IFN-γ对反应性T细胞的作用在内的炎症事件控制着记忆性CD8⁺T细胞的发育速度。