Cytokine-facilitated priming of CD8+T cell responses by DNA vaccination
Cytokine-facilitated priming of CD8+T cell responses by DNA vaccination
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DOI：
10.1007/s00109-002-0395-6
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发表时间：
2003-02-01
影响因子：
4.7
通讯作者：
Schirmbeck, R
中科院分区：
文献类型：
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作者：
Kwissa, M;Kröger, A;Schirmbeck, R
质粒DNA接种引起的免疫反应可以通过细胞因子编码质粒的共递送来增强和调节。我们研究了用基因枪注射DNA疫苗肌肉内或皮内是否通过共递送细胞因子编码质粒增强了细胞毒性T淋巴细胞（CTL）对乙型肝炎表面抗原（HBsAg）的反应。从一组被测试的细胞因子质粒中，只有小鼠ifn β、IL-15和GM-CSF编码质粒显示出效果。用1杯编码细胞内HBsAg（大LS）的质粒DNA进行皮内基因枪接种，当编码IFNbeta、IL15或GM-CSF的质粒共递送时，CTL启动增强；当注射编码分泌HBsAg（小S）的DNA疫苗时，没有观察到这种情况。肌肉注射低剂量（5杯）编码大HBsAg的DNA疫苗，在没有细胞因子、IFNbeta或il15编码质粒的情况下，不能启动CTL。然而，与编码质粒DNA的GM-CSF共递送可通过细胞毒性试验或通过确定特异性诱导IFNgamma产生的l -d限制性CD8(+) T细胞的频率检测到有效的特异性CTL免疫。GM-CSF编码质粒与DNA疫苗的共递送进一步增强了CTL对HBsAg亚显性、d- d限制性表位的引物。因此，细胞因子编码质粒对DNA疫苗启动CTL的辅助作用是复杂的，并取决于：(a)共同递送的细胞因子（或细胞因子组合）的类型，(b) DNA疫苗的类型（细胞内还是分泌）和剂量（1-50杯），(c) DNA疫苗递送方法（“裸”还是颗粒包裹DNA），以及(d) DNA疫苗递送途径（肌肉内还是皮内）。
Immune responses elicited by plasmid DNA vaccination can be enhanced and modulated by codelivery of cytokine-encoding plasmids. We studied whether priming of cytotoxic T lymphocyte (CTL) responses against hepatitis B surface antigen (HBsAg) by DNA vaccines injected either intramusculary or intradermally with the gene gun is enhanced by codelivery of cytokine-encoding plasmids. From a panel of tested cytokine plasmids only mouse IFNbeta, IL-15, and GM-CSF encoding plasmids showed an effect. Intradermal gene gun vaccination with 1 mug plasmid DNA encoding intracellular HBsAg (large LS) showed enhanced CTL priming when IFNbeta, IL15, or GM-CSF encoding plasmids were codelivered; this was not observed when a DNA vaccine encoding secreted HBsAg (small S) was injected. Intramuscular injection of low (5 mug) doses of a DNA vaccine encoding large HBsAg did not prime CTL when delivered without cytokines, with IFNbeta or IL15-encoding plasmids. However, codelivery with GM-CSF encoding plasmid DNA primed potent, specific CTL immunity detected either in a cytotoxic assay or by determining the frequency of L-d-restricted CD8(+) T cells specifically inducible to IFNgamma production. The codelivery of GM-CSF encoding plasmids with the DNA vaccine furthermore enhanced CTL priming to a subdominant, D-d-restricted epitope of HBsAg. The adjuvant effect of cytokine-encoding plasmids on CTL priming by DNA vaccines is thus complex and depends on: (a) the type of cytokine (or combination of cytokines) codelivered, (b) the type (intracellular vs. secreted) and dose (1-50 mug) of the DNA vaccine, (c) the method of DNA vaccine delivery ("naked" vs. particle-coated DNA), and (d) the (intra-muscular vs. intradermal) route of delivery of the DNA vaccine.