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分枝杆菌热休克蛋白诱导的血液T淋巴细胞亚群及细胞因子模式:结节病与结核病及健康对照的比较

Mycobacterial heat shock protein-induced blood T lymphocytes subsets and cytokine pattern: comparison of sarcoidosis with tuberculosis and healthy controls.

作者信息

Dubaniewicz Anna, Trzonkowski Piotr, Dubaniewicz-Wybieralska Mirosława, Dubaniewicz Andrzej, Singh Mahavir, Myśliwski Andrzej

机构信息

Department of Pathophysiology, Medical University of Gdańsk, Gdańsk, Poland.

出版信息

Respirology. 2007 May;12(3):346-54. doi: 10.1111/j.1440-1843.2007.01076.x.

Abstract

BACKGROUND AND OBJECTIVE

Sarcoidosis (SA) is a disorder of unknown aetiology. Mycobacterium tuberculosis heat shock proteins (Mtb-hsp) have been considered as causative agents of SA. The role of Mtb-hsp in the immune response in SA has not been investigated.

METHODS

Mtb-hsp-stimulated T-cell subsets and Th1/Th2 cytokine patterns in the supernatant from peripheral blood mononuclear cell cultures from 22 SA patients, 20 tuberculosis (TB) patients and 20 healthy volunteers were compared using flow cytometry.

RESULTS

In unstimulated cultures, a significantly higher percentage of CD8(+)alphabeta(+)T-cells were present in SA versus controls. Similarly there was a significantly increased IL-6 and decreased IL-4 level in SA and significantly lower INF-gamma, IL-2, IL-4, IL-10 production in TB versus controls. After Mtb-hsp stimulation, there was a significantly increased TNF-alpha, IL-6, IL-10 and decreased INF-gamma, IL-2, IL-4 production in SA and significantly increased TNF-alpha, IL-6 concentrations in TB versus controls. CD8(+)gammadelta(+)IL-4(+)T-cells were detected significantly less often in Mtb-hsp-induced cultures in SA versus controls. Comparing SA versus TB, CD4(+)gammadelta(+)TCR-cells were significantly increased in Mtb-hsp-induced cultures in TB versus controls and SA. Before stimulation, significantly increased IL-6, IL-10 and decreased IL-4 level in SA versus TB was revealed, whereas Mtb-hsp stimulation caused significantly increased IL-10 and decreased IL-4 concentrations in SA.

CONCLUSIONS

After Mtb-hsp stimulation, increased levels of pro-inflammatory cytokines, TNF-alpha and IL-6 were found in sera from SA and TB patients in comparison with healthy controls; SA patients demonstrated the lowest levels of IL-4 and the highest levels of IL-10.

摘要

背景与目的

结节病(SA)是一种病因不明的疾病。结核分枝杆菌热休克蛋白(Mtb-hsp)被认为是结节病的致病因素。Mtb-hsp在结节病免疫反应中的作用尚未得到研究。

方法

使用流式细胞术比较了22例结节病患者、20例结核病(TB)患者和20名健康志愿者外周血单个核细胞培养上清液中Mtb-hsp刺激的T细胞亚群和Th1/Th2细胞因子模式。

结果

在未刺激的培养物中,与对照组相比,结节病患者中CD8(+)αβ(+)T细胞的百分比显著更高。同样,结节病患者中IL-6水平显著升高,IL-4水平降低,而与对照组相比,结核病患者中INF-γ、IL-2、IL-4、IL-10的产生显著降低。Mtb-hsp刺激后,与对照组相比,结节病患者中TNF-α、IL-6、IL-10显著增加,INF-γ、IL-2、IL-4产生减少,结核病患者中TNF-α、IL-6浓度显著增加。与对照组相比,在结节病患者中Mtb-hsp诱导的培养物中CD8(+)γδ(+)IL-4(+)T细胞的检测频率显著降低。比较结节病与结核病,在Mtb-hsp诱导的培养物中,与对照组和结节病相比,结核病患者中CD4(+)γδ(+)TCR细胞显著增加。刺激前,与结核病相比,结节病患者中IL-6、IL-10显著增加,IL-4水平降低,而Mtb-hsp刺激导致结节病患者中IL-10显著增加,IL-4浓度降低。

结论

与健康对照组相比,Mtb-hsp刺激后,结节病和结核病患者血清中促炎细胞因子TNF-α和IL-6水平升高;结节病患者IL-4水平最低,IL-10水平最高。

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