Live attenuated yellow fever 17D infects human DCs and allows for presentation of endogenous and recombinant T cell epitopes.
Live attenuated yellow fever 17D infects human DCs and allows for presentation of endogenous and recombinant T cell epitopes.
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DOI：
10.1084/jem.20051352
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发表时间：
2005-11-07
期刊：
影响因子：
--
通讯作者：
Rice CM
中科院分区：
文献类型：
--
作者：
Barba-Spaeth G;Longman RS;Albert ML;Rice CM
黄热病(YF)17D疫苗是目前最成功的减毒活疫苗之一。一次免疫既能诱导持久中和抗体，又能诱导YF特异性T细胞反应。令人惊讶的是，这种强大免疫力的机制尚未得到解决。鉴于最近一些报道表明黄病毒与树突状细胞(DC)相互作用，我们研究了YF17D与DC相互作用的机制以及这种相互作用在产生T细胞免疫中的重要性。我们的结果表明，YF17D可以感染未成熟和成熟的人DC。病毒进入依赖于钙离子，但它不依赖于DC-SIGN以及DC表面表达的多种整合素。与细胞系感染相似，幼龄DC的YF感染是一种细胞病变。虽然感染本身不能在体外诱导DC成熟，但肿瘤坏死因子-α诱导的成熟保护DC免受YF诱导的细胞病变。此外，我们发现感染YF17D或携带重组表位的YF17D的DC可以加工和呈递抗原用于CD8+T细胞的刺激。这些发现提供了对与高效YF17D疫苗相关的免疫学机制的洞察，可能会指导有效的疫苗设计。
The yellow fever (YF) 17D vaccine is one of the most successful live attenuated vaccines available. A single immunization induces both long-lasting neutralizing antibody and YF-specific T cell responses. Surprisingly, the mechanism for this robust immunity has not been addressed. In light of several recent reports suggesting flavivirus interaction with dendritic cells (DCs), we investigated the mechanism of YF17D interaction with DCs and the importance of this interaction in generating T cell immunity. Our results show that YF17D can infect immature and mature human DCs. Viral entry is Ca2+ dependent, but it is independent of DC-SIGN as well as multiple integrins expressed on the DC surface. Similar to infection of cell lines, YF infection of immature DCs is cytopathic. Although infection itself does not induce DC maturation in vitro, TNF-α–induced maturation protects DCs from YF-induced cytopathogenicity. Furthermore, we show that DCs infected with YF17D or YF17D carrying a recombinant epitope can process and present antigens for CD8+ T cell stimulation. These findings offer insight into the immunologic mechanisms associated with the highly capable YF17D vaccine that may guide effective vaccine design.
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