Quantitative and qualitative analysis of the balance between type 1 and type 2 cytokine-producing CD8- and CD8+ T cells in systemic lupus erythematosus

Quantitative and qualitative analysis of the balance between type 1 and type 2 cytokine-producing CD8- and CD8+ T cells in systemic lupus erythematosus
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DOI:
10.1006/jaut.2001.0525
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发表时间:
2001-09-01
影响因子:
12.8
通讯作者:
Powell, RJ
Powell, RJ
中科院分区:
医学1区
文献类型:
--
作者:
Amel-Kashipaz, MR;Huggins, ML;Powell, RJ

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应用细胞内丙氨酸染色技术研究了系统性红斑狼疮(SLE)患者和正常人的CD 8(-)和CD 8(+)T细胞产生I型(IFN-γ、IL-2)和2型(IL-4、IL-5、IL-10、IL-13)细胞因子的情况。这种流式细胞术方法有助于分析表面标志物和细胞质细胞因子,短期(6小时)培养后,有或没有佛波醇肉豆蔻酸酯乙酸酯和离子霉素(PMA/I)刺激。在SLE患者中,与对照组相比,更多未受刺激的T细胞产生IL-10;未受刺激的细胞中未检测到其他细胞因子。SLE患者的IL-10分泌性T细胞的百分比在PMA/I刺激后没有显著增加。SLE患者CD 8(-)T细胞胞内IL-4染色的平均荧光强度(MIF)显著高于对照组。与对照组相比,SLE患者的CD 8(-)和CD 8(+)T细胞在PMA/I刺激后分泌IFN-γ的数量显著减少。SLE患者与对照组之间的MIF和IL-2、IL-5和IL-13分泌细胞亚群的百分比无显著差异。这些发现表明,SLE患者的T细胞已经在体内被刺激产生IL-10,这可能导致在PMA/I刺激后观察到的分泌IFN-γ的CD 8(-)和CD 8(+)T细胞的下调。因此,SLE患者中Th 1和Tc 1细胞的群体大小减少,而SLE患者中Th 2细胞的效应子功能(关于IL-4产生)增强。此外,尽管SLE患者的Th 1/Th 2和Tc 1/Tc 2之间的平衡被破坏,但其仅明显偏向于Th 2亚群。(C)北京:科学出版社.
The production of type I (IFN-gamma, IL-2) and type 2 (IL-4, IL-5, IL-10, IL-13) cytokines by CD8(-) and CD8(+) T cells from systemic lupus erythematosus (SLE) patients and normal subjects was investigated using an intracellular cytokine-staining technique. This flow cytometric method facilitates analysis of both surface markers and cytoplasmic cytokines, after a short term (6h) culture with or without phorbol myristate acetate and ionomycin (PMA/I) stimulation. In SLE patients, more unstimulated T cells produced IL-10 in comparison with controls; other cytokines were not detected in unstimulated cells. The percentage of IL-10-secreting T cells did not significantly increase after PMA/I stimulation of cells from SLE patients. The mean intensity of fluorescence (MIF) of intracellular IL-4 staining was significantly higher in CD8(-) T cells of SLE patients than controls. Significantly fewer CD8(-) and CD8(+) T cells from SLE patients secreted IFN-gamma after PMA/I stimulation compared with controls. The MIF and percentage of IL-2, IL-5, and IL-13-secreting cell subsets were not significantly different between SLE patients and controls. These findings indicate that T cells of SLE patients are already stimulated to produce IL-10 in vivo, which may result in downregulation of IFN-gamma secreting CD8(-) and CD8(+) T cells observed following PMA/I stimulation. Thus, the population size of Th1 and Tc1 cells are reduced in SLE patients whereas the effector function of Th2 cells, with respect to IL-4 production, is enhanced in SLE patients. Furthermore, although the balance between Th1/Th2 and between Tc1/Tc2 is disrupted in SLE patients, it is significantly biased in favour of the Th2 subset only. (C) 2001 Academic Press.