中文摘要：研究表明，明矾作为佐剂在免疫后可以激活免疫抑制反应机制，从而限制了其激活Th1反应的能力；这一过程中，受到限制过多免疫反应的重要细胞因子之一是IL-10。体外将明矾注射到引流淋巴结细胞中能够增强IL-10的分泌。同时，在注射位点，巨噬细胞和树突状细胞也是IL-10的主要分泌源。IL-10信号缺失后，明矾诱导的细胞无法渗入注射位点，但会增强抗原特异性Th1反应；与这一调控作用相对应的是，IL-10缺陷型小鼠采用明矾佐剂免疫后，抗原特异性IgG1抗体浓度不会产生变化。总而言之，明矾注射能够提高IL-10的浓度，从而阻止Th1反应，这就解释了明矾作为佐剂应用时不能有效诱导产生保护性Th1免疫的机制。
外文摘要：The effectiveness of many vaccines licensed for clinical use relates to the induction of neutralising antibodies, facilitated by the inclusion of vaccine adjuvants, particularly alum. However, the ability of alum to preferentially promote humoral rather than cellular, particularly Th1-type responses, is not well understood. We demonstrate that alum activates immunosuppressive mechanisms following vaccination, which limit its capacity to induce Th1 responses. One of the key cytokines limiting excessive immune responses is IL-10. Injection of alum primed draining lymph node cells for enhanced IL-10 secretion ex vivo. Moreover, at the site of injection, macrophages and dendritic cells were key sources of IL-10 expression. Alum strongly enhanced the transcription and secretion of IL-10 by macrophages and dendritic cells. The absence of IL-10 signalling did not compromise alum-induced cell infiltration into the site of injection, but resulted in enhanced antigen-specific Th1 responses after vaccination. In contrast to its decisive regulatory role in regulating Th1 responses, there was no significant change in antigen-specific IgG1 antibody production following vaccination with alum in IL-10-deficient mice. Overall, these findings indicate that injection of alum promotes IL-10, which can block Th1 responses and may explain the poor efficacy of alum as an adjuvant for inducing protective Th1 immunity.
外文关键词： Aluminium adjuvant, IL-10, IFN-gamma, Th1, Vaccination
作者：Oleszycka, E; McCluskey, S; Sharp, FA; Munoz-Wolf, N; Hams, E; Gorman, AL; Fallon, PG; Lavelle, EC
作者单位：爱尔兰都柏林大学圣三一学院
期刊名称：EUROPEAN JOURNAL OF IMMUNOLOGY
期刊影响因子：4.227
出版年份：2018
出版刊次：4
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