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使用双顺反子白细胞介素-4报告基因小鼠来鉴定用铝佐剂免疫后表达白细胞介素-4的细胞。

Using bicistronic IL-4 reporter mice to identify IL-4 expressing cells following immunisation with aluminium adjuvant.

作者信息

McDonald Fiona, Mohrs Markus, Brewer James

机构信息

Division of Immunology, Infection & Inflammation, University of Glasgow, Glasgow G11 6NT, UK.

出版信息

Vaccine. 2006 Jun 29;24(26):5393-9. doi: 10.1016/j.vaccine.2006.03.049. Epub 2006 Mar 31.

Abstract

The Th2 dominated immune response induced by aluminium adjuvants remains a major limitation to their application to modern vaccines. Previous studies have shown that while these adjuvants can initiate Th2 responses in mice with disrupted IL-4 production or IL-4 signalling, a strong Th1 response becomes evident in these situations, suggesting that the main function of IL-4 in the response to aluminium adsorbed antigens is to antagonise Th1 induction. In this study we have employed the recently described, 4get reporter mice, that express GFP as part of a bicistronic IL-4-IRES-GFP mRNA, to identify IL-4 expressing cells in situ during an aluminium adjuvant-induced Th2 responses. These preliminary studies implicate conventional CD4+ T cells as the sole potential producers of IL-4 following immunisation with antigen prepared in aluminium adjuvants. Furthermore, as GFP positive cells are first detected in the lymph node, our studies indicate that these cells may act to block induction of Th1 responses by aluminium adjuvants. We conclude that devising strategies to block the effects of IL-4 production by these cells will facilitate the rational design of vaccine adjuvants that induce Th1 responses.

摘要

铝佐剂诱导的以Th2为主导的免疫反应仍然是其应用于现代疫苗的主要限制因素。先前的研究表明,虽然这些佐剂能在白细胞介素4(IL-4)产生或IL-4信号传导被破坏的小鼠中引发Th2反应,但在这些情况下,强烈的Th1反应会变得明显,这表明IL-4在对铝吸附抗原的反应中的主要功能是拮抗Th1的诱导。在本研究中,我们使用了最近描述的4get报告小鼠,该小鼠表达绿色荧光蛋白(GFP)作为双顺反子IL-4-内部核糖体进入位点(IRES)-GFP mRNA的一部分,以在铝佐剂诱导的Th2反应过程中原位鉴定表达IL-4的细胞。这些初步研究表明,在用铝佐剂制备的抗原免疫后,传统的CD4 + T细胞是IL-4的唯一潜在产生者。此外,由于GFP阳性细胞首先在淋巴结中被检测到,我们的研究表明这些细胞可能起到阻止铝佐剂诱导Th1反应的作用。我们得出结论,设计策略来阻断这些细胞产生IL-4的作用将有助于合理设计诱导Th1反应的疫苗佐剂。

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