The novel synthetic immune response modifier R-848 (Resiquimod) shifts human allergen-specific CD4+ TH2 lymphocytes into IFN-γ-producing cells
The novel synthetic immune response modifier R-848 (Resiquimod) shifts human allergen-specific CD4+ TH2 lymphocytes into IFN-γ-producing cells
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DOI：
10.1067/mai.2003.102
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发表时间：
2003-02-01
影响因子：
14.2
通讯作者：
Parronchi, P
中科院分区：
文献类型：
--
作者：
Brugnolo, F;Sampognaro, S;Parronchi, P
背景：在实验模型中，咪唑喹啉通过先天免疫细胞上的 Toll 样受体信号传导表现出多种免疫调节活性。 目的：我们研究的目的是研究 R-848（Resiquimod）（一种属于咪唑喹啉家族的小分子量合成化合物，以其显着延缓复发性生殖器疱疹发作的能力而闻名）是否具有多种免疫调节活性。 动物和人类的损伤，至少在体外可能影响人类半抗原或过敏原特异性 T 细胞的细胞因子产生情况。方法：氨苄西林和 Der p1 特异性 T 细胞系源自过敏性供体的外周血，在不存在或存在 R-848 的情况下，通过流式细胞术在单细胞水平评估其产生 IL-4 的能力 结果：R-848 诱导半抗原和过敏原特异性循环 T 细胞（包括 T(H)2 效应细胞）产生 IFN-gamma，甚至失去产生 IL-4 的能力，从而将其细胞因子产生表型转变为 0 型 (T(H)0) 甚至 T(H)1 型。这种效应与 CD14(+) 细胞产生 IL-12、IFN-α、IL-18、TNF-α、IL-10 和 IL-15 的增加以及产生 IFN-γ 的 CD3-CD16(+)（自然杀伤）细胞比例的增加有关。结论：这些结果表明 R-848 以及可能的其他咪唑喹啉类化合物， 鉴于用于治疗过敏性疾病的新型过敏原特异性免疫治疗方案，可用作佐剂。
Background: In experimental models, imidazoquinolines exhibit several immunomodulatory activities via Toll-like receptor signaling on cells of the innate immunity.Objective: The aim of our study was to investigate whether R-848 (Resiquimod), a small-molecular-weight synthetic compound belonging to the imidazoquinoline family and known for its ability to substantially delay the onset of recurrent genital herpes lesions in both animals and human beings, could influence, at least in vitro, the cytokine production profile of human hapten- or allergen-specific T cells.Methods: Ampicillin- and Der p1-specific T-cell lines were derived from peripheral blood of allergic donors in the absence or presence of R-848 and assessed by flow cytometry at the single-cell level for their ability to produce IL-4 and/or IFN-gamma.Results: R-848 induced both hapten- and allergen-specific circulating T cells, including T(H)2 effectors, to produce IFN-gamma and even to lose the ability to produce IL-4, thus shifting their phenotype of cytokine production to a type 0 (T(H)0) or even T(H)1 profile. This effect was associated with an increase in the production of IL-12, IFN-alpha, IL-18, TNF-alpha, IL-10, and IL-15 by CD14(+) cells, as well as an increase in the proportions of IFN-gamma-producing CD3-CD16(+) (natural killer) cells.Conclusions: These results suggest that R-848, and probably other imidazoquinolines, might be used as adjuvants in view of novel allergen-specific immunotherapeutic regimens for the treatment of allergic disorders.