Using bicistronic IL-4 reporter mice to identify IL-4 expressing cells following immunisation with aluminium adjuvant
Using bicistronic IL-4 reporter mice to identify IL-4 expressing cells following immunisation with aluminium adjuvant
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DOI：
10.1016/j.vaccine.2006.03.049
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发表时间：
2006-06-29
期刊：
影响因子：
5.5
通讯作者：
Brewer, James
中科院分区：
文献类型：
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作者：
McDonald, Fiona;Mohrs, Markus;Brewer, James
铝佐剂诱导的Th 2主导的免疫应答仍然是其应用于现代疫苗的主要限制。先前的研究已经表明，虽然这些佐剂可以在IL-4产生或IL-4信号传导被破坏的小鼠中启动Th 2应答，但在这些情况下，强烈的Th 1应答变得明显，这表明IL-4在对铝吸附抗原的应答中的主要功能是拮抗Th 1诱导。在这项研究中，我们采用了最近描述的，4get报告小鼠，表达GFP作为一个双顺反子IL-4-IRES-GFP mRNA的一部分，以确定IL-4表达细胞在原位铝佐剂诱导的Th 2反应。这些初步研究表明，在用铝佐剂中制备的抗原免疫后，常规CD 4 + T细胞是IL-4的唯一潜在生产者。此外，由于GFP阳性细胞首先在淋巴结中检测到，我们的研究表明，这些细胞可能起到阻断铝佐剂诱导Th 1应答的作用。我们的结论是，设计策略来阻止这些细胞产生IL-4的影响，将有助于诱导Th 1反应的疫苗佐剂的合理设计。(c)2006年由Elsevier Ltd.出版
The Th2 dominated immune response induced by aluminium adjuvants remains a major limitation to their application to modem 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. (c) 2006 Published by Elsevier Ltd.