Th1‐biased immune responses induced by DNA‐based immunizations are mediated via action on professional antigen‐presenting cells to up‐regulate IL‐12 production
Th1‐biased immune responses induced by DNA‐based immunizations are mediated via action on professional antigen‐presenting cells to up‐regulate IL‐12 production
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基于 DNA 的免疫诱导的 Th1 偏向免疫反应是通过作用于专业抗原呈递细胞来介导的，从而上调 IL-12 的产生
DOI：
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发表时间：
2000
影响因子：
4.6
通讯作者：
J. Fukushima
中科院分区：
文献类型：
--
作者：
Y. Asakura;L.‐J. Liu;N. Shono;J. Hinkula;A. Kjerrström;I. Aoki;K. Okuda;B. Wahren;J. Fukushima
已经描述了基于DNA的免疫在授予对包括人类免疫缺陷病毒1型(HIV-1)在内的某些微生物病原体的保护性免疫方面的效果。与传统疫苗相比，基于DNA的免疫的潜在优势很大程度上是因为它能够有效地诱导针对编码抗原的Th1偏向免疫反应。我们使用编码 -1干扰素gp160cDNA的DNA疫苗和携带小鼠干扰素-γ的真核表达载体，描述了基于DNA的免疫是如何诱导Th1偏向的免疫反应的。将携带免疫刺激序列(ISS)和目的基因的真核表达载体(DNA疫苗)导入专业抗原提呈细胞(APC)，可诱导IL-12mRNA的反式激活，从而产生针对编码抗原的特异性Th1免疫应答。异位干扰素-γ共表达系统可显著上调DNA免疫诱导的Th1偏向免疫应答，这种增强是通过作用于专业抗原提呈细胞上调IL-12的产生而实现的。综上所述，基于DNA的免疫诱导的偏向Th1的免疫反应似乎是通过作用于专业抗原提呈细胞产生IL-12来介导的。有趣的是，该模型与之前在感染单核细胞增多性李斯特菌时描述的模型惊人地相似，李斯特菌是一种细胞内的革兰氏阳性细菌，可以诱导强烈的偏向Th1的免疫反应。结果表明，DNA免疫模仿了微生物自然感染的某些方面，如减毒疫苗，这反过来为为什么基于DNA的免疫如此有效地诱导对这些微生物病原体的保护性免疫提供了理论基础。
The efficacy of DNA‐based immunization in conferring protective immunity against certain microbial pathogens including human immunodeficiency virus type 1 (HIV‐1) has been described. The potential advantage of DNA‐based immunization over the traditional vaccines largely results from its capacity to efficiently induce Th1‐biased immune responses against an encoded antigen. We describe how Th1‐biased immune responses are induced by DNA‐based immunization, using a DNA vaccine construct encoding HIV‐1 gp160 cDNA and an eukaryotic expression plasmid carrying murine IFN‐γ cDNA. Transfection of an eukaryotic expression plasmid carrying immunostimulatory sequences (ISS) as well as a gene of interest (DNA vaccine) into professional antigen presenting cells (APC) induced transactivation of IL‐12 mRNA, which resulted in antigen‐specific Th1‐biased immune responses against the encoded antigen. Th1‐biased immune responses induced by DNA‐based immunization were substantially upregulated by a codelivery of an ectopic IFN‐γ expression system, and this augmentation was mediated via action on professional antigen presenting cells to upregulate IL‐12 production. Taken together, it appears likely that Th1‐biased immune responses induced by DNA‐based immunization are mediated via action on professional antigen‐presenting cells to produce IL‐12. Interestingly, the model provided strikingly resembles that previously described in infection with Listeria monocytogenes, an intracellular Gram‐positive bacterium that induces strong Th1‐biased immune responses. The result suggests that DNA‐based immunization mimics certain aspects of natural infection with microbial organisms like attenuated vaccines, which in turn provides a rationale to the question of why DNA‐based immunization so efficiently induces protective immunity against these microbial pathogens.
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影响因子：
3.7
作者：
Choi,AH;Knowlton,DR;McNeal,MM;Ward,RL
通讯作者：
Ward,RL
影响因子：
56.9
作者：
KARUPIAH, G;XIE, QW;MACMICKING, JD
通讯作者：
MACMICKING, JD
影响因子：
56.9
作者：
HUANG, S;HENDRIKS, W;AGUET, M
通讯作者：
AGUET, M
DOI：
10.1073/pnas.88.2.542
发表时间：
1991-01-01
影响因子：
11.1
作者：
GIRARD, M;KIENY, MP;FULTZ, PN
通讯作者：
FULTZ, PN
影响因子：
56.9
作者：
HSIEH, CS;MACATONIA, SE;MURPHY, KM
通讯作者：
MURPHY, KM