Activation of dendritic cells and induction of CD4+ T cell differentiation by aluminum-containing adjuvants
Activation of dendritic cells and induction of CD4+ T cell differentiation by aluminum-containing adjuvants
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DOI：
10.1016/j.vaccine.2007.03.045
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发表时间：
2007-06-06
期刊：
影响因子：
5.5
通讯作者：
HogenEsch, Harm
中科院分区：
文献类型：
--
作者：
Sokolovska, Anna;Hem, Stanley L.;HogenEsch, Harm
含铝佐剂被广泛用于获得许可的人类和兽医疫苗。然而，这些佐剂增强免疫反应并主要刺激T(H)2体液免疫反应的机制尚不清楚。本研究观察了氢氧化铝和磷酸铝佐剂对小鼠树突状细胞(DC)抗原提呈、共刺激分子和细胞因子表达的影响，以及DC诱导T辅助细胞分化的能力。用卵清蛋白(OVA)冲击的树突状细胞(DC)比单独用OVA冲击的树突状细胞(DC)更有效地吸附到含铝佐剂上激活抗原特异性T细胞。氢氧化铝佐剂的效果明显强于磷酸铝佐剂。两种含铝佐剂均能显着增加DC表面CD86的表达，但仅氢氧化铝佐剂可诱导中等程度的CD80表达。含铝佐剂通过激活caspase-1刺激DC释放IL-1β和IL-18。DC与内毒素和卵清蛋白共同孵育后，可诱导初始CD4(+)T细胞分化为TH1。相比之下，树突状细胞与铝/卵清蛋白激活的CD4(+)T细胞孵育后，分泌IL-4、IL-5和干扰素-γ。添加中和抗IL-1β抗体可减少IL-5的产生，添加抗IL-1β抗体可同时减少IL-4和IL-5的产生。通过抑制caspase-1抑制树突状细胞分泌IL-1β和IL-18，也导致CD4(+)T细胞分泌IL-4和IL-5明显减少。这些结果表明，含铝佐剂通过分泌IL-1β和IL-18来激活DC并影响其直接T(H)1和T(H)2反应的能力。(C)2007爱思唯尔有限公司。保留所有权利。
Aluminum-containing adjuvants are widely used in licensed human and veterinary vaccines. However, the mechanism by which these adjuvants enhance the immune response and predominantly stimulate a T(H)2 humoral immune response is not well understood. In this study, the effects of aluminum hydroxide and aluminum phosphate adjuvants on antigen presentation, expression of costimulatory molecules and cytokines by mouse dendritic cells (DCs) and the ability of DCs to induce T helper cell differentiation were investigated. Dendritic cells pulsed with ovalbumin (OVA) adsorbed to aluminum-containing adjuvants activated antigen-specific T cells more effectively than DCs pulsed with OVA alone. Aluminum hydroxide adjuvant had a significantly stronger effect than aluminum phosphate adjuvant. Both aluminum-containing adjuvants significantly increased the expression of CD86 on DCs but only aluminum hydroxide adjuvant also induced moderate expression of CD80. Aluminum-containing adjuvants stimulated the release of IL-1 beta and IL-18 from DCs via caspase-1 activation. DCs incubated with LPS and OVA induced TH1 differentiation of naive CD4(+) T cells. In contrast, DCs incubated with aluminum/OVA activated CD4(+) T cells to secrete IL-4 and IL-5 as well as IFN-gamma. Addition of neutralizing anti-IL-1 beta antibodies decreased IL-5 production and addition of anti-IL-1 beta antibodies decreased both IL-4 and IL-5 production. Inhibition of IL-1 beta and IL-18 secretion by DCs via inhibition of caspase-1 also led to a marked decrease of IL-4 and IL-5 by CD4(+) T cells. These results indicate that aluminum-containing adjuvants activate DCs and influence their ability to direct T(H)1 and T(H)2 responses through the secretion of IL-1 beta and IL-18. (C) 2007 Elsevier Ltd. All rights reserved.