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免疫疗法通过变应原刺激抑制Th1和Th2反应,但抑制Th2反应是与常年性变应性鼻炎免疫疗法临床疗效相关的更重要机制。

Immunotherapy suppresses both Th1 and Th2 responses by allergen stimulation, but suppression of the Th2 response is a more important mechanism related to the clinical efficacy of immunotherapy for perennial allergic rhinitis.

作者信息

Tanaka A, Ohashi Y, Kakinoki Y, Nakai Y

机构信息

Department of Otolaryngology, Osaka City University Medical School, Abeno, Japan.

出版信息

Scand J Immunol. 1998 Aug;48(2):201-11. doi: 10.1046/j.1365-3083.1998.00362.x.

DOI:10.1046/j.1365-3083.1998.00362.x
PMID:9716113
Abstract

Increased attention has recently been directed at the possibility that the clinical efficacy of immunotherapy might be elaborated by alteration of T-cell reactivity. However, there is no general agreement among different investigators regarding the effect of immunotherapy on Th-cell reactivity. Peripheral blood mononuclear cells (PBMCs) from 15 nonatopic subjects and 76 patients with perennial allergic rhinitis (18 untreated patients and 58 patients on immunotherapy) were cultured in the absence and in the presence of a major Dermatophagoides farinae allergen, Der f 1, and the levels of IgE, interleukin-5 (IL-5), interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) in the culture supernatants were determined. The difference between the absence and presence of Der f 1 was calculated to consider the Der f 1-dependent synthesis of IgE, IL-5, IFN-gamma and TNF-alpha. The levels of Der f 1-dependent synthesis of IgE, IL-5 and TNF-alpha were significantly higher in the untreated group than in the nonatopic group, whereas Der f 1-dependent synthesis of IFN-gamma was significantly lower in the untreated group than in the nonatopic group. Immunotherapy decreased the enhanced Der f 1-dependent synthesis of IgE, IL-5 and TNF-alpha, and further decreased the suppressed Der f 1-dependent synthesis of IFN-gamma as the therapy proceeded. The levels of Der f 1-dependent synthesis of IgE and IL-5 did not differ between nonatopic individuals and patients whose duration of immunotherapy was 10 or more years. The levels of Der f 1-dependent synthesis of IgE and IL-5, but not of IFN-gamma and TNF-alpha, were correlated significantly with the levels of symptom scores. In addition, the levels of Der f 1-dependent synthesis of IgE and IL-5, but not of IFN-gamma and TNF-alpha, differed significantly between good and poor responders. In conclusion, immunotherapy for perennial allergic rhinitis may possibly work via induction of tolerance or anergy of both Th1- and Th2 cells. However, our study is likely to support a view that the mechanisms responsible for the clinically beneficial effects of immunotherapy principally involve the tolerance of Th2- rather than Th1 cells. In addition, suppression of IgE synthesis is also likely to be linked to the clinical efficacy of immunotherapy for perennial allergic rhinitis.

摘要

最近,人们越来越关注免疫疗法的临床疗效可能通过改变T细胞反应性来实现这一可能性。然而,不同研究者对于免疫疗法对Th细胞反应性的影响尚未达成普遍共识。将15名非特应性受试者和76例常年性变应性鼻炎患者(18例未治疗患者和58例接受免疫疗法的患者)的外周血单个核细胞(PBMC)在不存在和存在主要粉尘螨过敏原Der f 1的情况下进行培养,并测定培养上清液中IgE、白细胞介素-5(IL-5)、干扰素-γ(IFN-γ)和肿瘤坏死因子-α(TNF-α)的水平。计算Der f 1存在与不存在时的差异,以考量Der f 1依赖性的IgE、IL-5、IFN-γ和TNF-α合成情况。未治疗组中Der f 1依赖性的IgE、IL-5和TNF-α合成水平显著高于非特应性组,而未治疗组中Der f 1依赖性的IFN-γ合成水平显著低于非特应性组。随着免疫疗法的进行,免疫疗法降低了增强的Der f 1依赖性的IgE、IL-5和TNF-α合成,并进一步降低了受抑制的Der f 1依赖性的IFN-γ合成。非特应性个体与免疫疗法持续时间为10年或更长时间的患者之间,Der f 1依赖性的IgE和IL-5合成水平没有差异。Der f 1依赖性的IgE和IL-5合成水平,但不包括IFN-γ和TNF-α的合成水平,与症状评分水平显著相关。此外,良好和不良应答者之间Der f 1依赖性的IgE和IL-5合成水平,但不包括IFN-γ和TNF-α的合成水平,存在显著差异。总之,常年性变应性鼻炎的免疫疗法可能通过诱导Th1和Th2细胞的耐受性或无反应性起作用。然而,我们的研究可能支持这样一种观点,即免疫疗法临床有益效果的机制主要涉及Th2细胞而非Th1细胞的耐受性。此外,IgE合成的抑制也可能与常年性变应性鼻炎免疫疗法的临床疗效相关。

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