皮下变应原免疫治疗可恢复人类树突状细胞固有免疫功能。
Subcutaneous allergen immunotherapy restores human dendritic cell innate immune function.
机构信息
The Division of Clinical Immunology, The Mount Sinai School of Medicine, 1425 Madison Avenue, New York, NY 10029, USA.
出版信息
Clin Exp Allergy. 2010 Jan;40(1):94-102. doi: 10.1111/j.1365-2222.2009.03388.x.
BACKGROUND
We recently reported that human blood dendritic cells from allergic subjects have impaired IFN-alpha production following toll-like receptor 9 (TLR9)-dependent innate immune stimulation. It is not known how subcutaneous allergen immunotherapy (SCIT) affects dendritic cell immune responses.
OBJECTIVE
The aim of this study is to determine how SCIT affects human dendritic cell function.
METHODS
Peripheral blood mononuclear cell (PBMC) and plasmacytoid dendritic cells (pDCs) were isolated from the blood of seven dust mite allergic subjects at baseline and upon reaching a standard SCIT maintenance dose that included dust mite and other aeroallergens. Cells were stimulated with various adaptive and innate immune receptor stimuli, or media alone for 20 h with secreted cytokine levels determined by ELISA. A portion of the cells were used to measure intracellular signalling proteins by flow cytometry. Humoral immune responses were measured from plasma.
RESULTS
SCIT resulted in a threefold increase in PBMC production of IFN-alpha in response to CpG at 100 nM (P=0.015) and at 500 nM (P=0.015), n=7. The predominant cell type known to produce IFN-alpha in response to CpG (CpG ODN-2216) and other TLR9 agonists is the pDC. As expected, a robust innate immune response from isolated pDCs was re-established among allergic subjects undergoing SCIT resulting in a fivefold increase in IFN-alpha production in response to CpG at 500 nM (P=0.046), n=7. In contrast, IL-6 production was unaffected by SCIT (P=0.468). Consistent with published reports, IgG4 blocking antibody increased 10-fold with SCIT (P=0.031), n=7. There was no significant increase in the frequency of pDCs or the expression of TLR9 that would account for the rise in IFN-alpha production.
CONCLUSIONS
Allergen immunotherapy increases dendritic cell TLR9-mediated innate immune function, which has previously been shown to be impaired at baseline in allergic subjects.
背景
我们最近报道称，在受到 Toll 样受体 9（TLR9）依赖性固有免疫刺激后，过敏性患者的人血树突状细胞产生 IFN-α的能力受损。目前尚不清楚皮下变应原免疫疗法（SCIT）如何影响树突状细胞的免疫反应。
目的
本研究旨在确定 SCIT 如何影响人类树突状细胞的功能。
方法
从 7 名尘螨过敏患者的血液中分离外周血单核细胞（PBMC）和浆细胞样树突状细胞（pDC），在达到包括尘螨和其他空气过敏原在内的 SCIT 维持剂量时。用各种适应性和固有免疫受体刺激物或单独的培养基刺激细胞 20 小时，通过 ELISA 测定分泌细胞因子的水平。一部分细胞用于通过流式细胞术测量细胞内信号蛋白。从血浆中测量体液免疫反应。
结果
SCIT 导致 PBMC 对 CpG（100 nM，P=0.015；500 nM，P=0.015）的 IFN-α产生增加了三倍，n=7。已知对 CpG（CpG ODN-2216）和其他 TLR9 激动剂产生 IFN-α的主要细胞类型是 pDC。正如预期的那样，接受 SCIT 的过敏患者中 pDC 的固有免疫反应得到了重新建立，导致对 CpG（500 nM，P=0.046）的 IFN-α产生增加了五倍，n=7。相比之下，IL-6 的产生不受 SCIT 的影响（P=0.468）。与已发表的报告一致，SCIT 使 IgG4 阻断抗体增加了 10 倍（P=0.031），n=7。TLR9 的表达或 pDC 的频率没有显著增加，这可以解释 IFN-α产生的增加。
结论
变应原免疫疗法增加了树突状细胞 TLR9 介导的固有免疫功能，而这在过敏患者的基线中已经显示受损。
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