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尘螨过敏性哮喘特异性免疫治疗过程中三个时间点的T细胞细胞因子模式

T-cell cytokine pattern at three time points during specific immunotherapy for mite-sensitive asthma.

作者信息

Majori M, Caminati A, Corradi M, Brianti E, Scarpa S, Pesci A

机构信息

Istituto di Clinica delle Malattie dell'Apparato Respiratorio dell'Università degli Studi; Centro di Allergologia e Immunologia Clinica dell'Azienda Unità Sanitaria Locale, Parma, Italy.

出版信息

Clin Exp Allergy. 2000 Mar;30(3):341-7. doi: 10.1046/j.1365-2222.2000.00701.x.

Abstract

BACKGROUND

Several lines of evidence indicate that specific immunotherapy may act by modifying the patterns of cytokines produced by helper T cells. However, different protocols have been used and different results obtained.

OBJECTIVES

To quantify the effect of specific immunotherapy on the TH1/TH2 T-cell cytokine pattern at the single cell level.

METHODS

We examined the interferon-gamma/interleukin-4 ratio in peripheral blood CD4+ and CD8+ T cells from 12 subjects with house dust mite-sensitive asthma using a flow cytometric method of intracellular cytokine detection. Cytokine production was determined following stimulation with phorbol myristate acetate/ionomycin, a policlonal activator. Subjects were examined at three occasions: before specific immunotherapy, after the 3-months dose increase phase and after 1 year of treatment. During the treatment year patients kept a diary in which they recorded: (a) symptoms of asthma according to a 0-3 grading (0 = absent, 1 = mild, 2 = moderate, 3 = severe); (b) number of puffs (100 microg) per day of salbutamol required to control symptoms; and (c) peak expiratory flow.

RESULTS

Specific immunotherapy improved clinical indices of disease activity including symptom scores and medication use during the treatment year, and had a marked effect in increasing the interferon-gamma/interleukin-4 ratio in peripheral blood CD4+ T cells already after the dose increase phase (5.47 +/- 1.5 vs 4.07 +/- 1.49%, P = 0.03) with and a further rise after 1 year's treatment (16.12 +/- 2.8 vs 4.07 +/- 1.49 and 16.12 +/- 2.8 vs 5.47 +/- 1.5%, P = 0.001 and P = 0.002, respectively). There were no significant changes in the interferon-gamma/interleukin-4 ratio in peripheral blood CD8+ T cells at the three times of the study.

CONCLUSIONS

These data add to view that the efficacy of specific immunotherapy may be attributed to a modified cytokine secretion of CD4+ T cells.

摘要

背景

多项证据表明,特异性免疫疗法可能通过改变辅助性T细胞产生的细胞因子模式发挥作用。然而,使用了不同的方案并获得了不同的结果。

目的

在单细胞水平上量化特异性免疫疗法对TH1/TH2 T细胞细胞因子模式的影响。

方法

我们采用细胞内细胞因子检测的流式细胞术方法,检测了12名对屋尘螨敏感的哮喘患者外周血CD4+和CD8+ T细胞中的干扰素-γ/白细胞介素-4比值。在用佛波酯肉豆蔻酸酯/离子霉素(一种多克隆激活剂)刺激后,测定细胞因子的产生。在三个时间点对受试者进行检查:特异性免疫疗法前、剂量增加3个月阶段后以及治疗1年后。在治疗期间,患者记录日记,记录:(a)根据0-3分级的哮喘症状(0 = 无,1 = 轻度,2 = 中度,3 = 重度);(b)控制症状所需的每日沙丁胺醇(100微克)喷雾次数;以及(c)呼气峰值流速。

结果

特异性免疫疗法改善了疾病活动的临床指标,包括治疗期间的症状评分和药物使用情况,并且在剂量增加阶段后,对外周血CD4+ T细胞中的干扰素-γ/白细胞介素-4比值就有显著影响(5.47±1.5对4.07±1.49%,P = 0.03),治疗1年后进一步升高(16.12±2.8对4.07±1.49以及16.12±2.8对5.4 7±1.5%,P分别为0.001和0.002)。在研究的三个时间点,外周血CD8+ T细胞中的干扰素-γ/白细胞介素-4比值没有显著变化。

结论

这些数据进一步支持了特异性免疫疗法的疗效可能归因于CD4+ T细胞细胞因子分泌改变的观点。

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