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由肽脉冲树突状细胞释放的外泌体进行的抗原呈递不会被活性细胞毒性T淋巴细胞的存在所抑制。

Antigen presentation by exosomes released from peptide-pulsed dendritic cells is not suppressed by the presence of active CTL.

作者信息

Luketic Lea, Delanghe Jordan, Sobol Paul T, Yang Pingchang, Frotten Erin, Mossman Karen L, Gauldie Jack, Bramson Jonathan, Wan Yonghong

机构信息

Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.

出版信息

J Immunol. 2007 Oct 15;179(8):5024-32. doi: 10.4049/jimmunol.179.8.5024.

Abstract

Despite the potency of dendritic cells (DCs) as a vaccine carrier, they are short-lived and sensitive to CTL-mediated elimination. Thus, it is believed that the longevity of Ag presentation by peptide-pulsed DC is limited in vivo. Surprisingly, however, we found that although the majority of injected DCs disappeared from the draining lymph nodes within 7 days, Ag presentation persisted for at least 14 days following DC immunization. This prolonged Ag presentation was not mediated by the remaining injected DCs or through Ag transfer to endogenous APCs. We provide evidence that exosomes released by DCs might be responsible for the persistence of Ag presentation. Functional exosomes could be recovered from the draining lymph nodes of C57BL/6 mice following DC vaccination and, in contrast to DCs, T cell stimulation by exosomes in vivo was not affected by the presence of CTL. Our findings demonstrate that Ag presentation following delivery of DC vaccines persists for longer than expected and indicate that the exosome may play a previously unrecognized role in Ag presentation following DC vaccination. Furthermore, our study reinforces the application of exosomes as a vaccination platform and suggests that exosome-based vaccines may be advantageous for booster immunizations due to their resistance to CTL.

摘要

尽管树突状细胞(DCs)作为疫苗载体具有强大的功能,但它们寿命短暂且对CTL介导的清除敏感。因此,人们认为肽脉冲DC在体内呈递抗原的持续时间有限。然而,令人惊讶的是,我们发现尽管大多数注射的DC在7天内从引流淋巴结中消失,但DC免疫后抗原呈递持续了至少14天。这种延长的抗原呈递不是由剩余的注射DC介导的,也不是通过抗原转移到内源性APC介导的。我们提供证据表明,DC释放的外泌体可能是抗原呈递持续存在的原因。功能性外泌体可以从C57BL/6小鼠DC疫苗接种后的引流淋巴结中回收,与DC不同,体内外泌体对T细胞的刺激不受CTL存在的影响。我们的研究结果表明,DC疫苗接种后抗原呈递持续的时间比预期的更长,这表明外泌体可能在DC疫苗接种后的抗原呈递中发挥了以前未被认识到的作用。此外,我们的研究加强了外泌体作为疫苗接种平台的应用,并表明基于外泌体的疫苗由于其对CTL的抗性,可能对加强免疫有益。

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