IFN-γ but not IL-4 T cells of the asthmatic bronchial wall show increased incidence of apoptosis
IFN-γ but not IL-4 T cells of the asthmatic bronchial wall show increased incidence of apoptosis
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DOI：
10.1046/j.1365-2222.2001.01099.x
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发表时间：
2001-05-01
影响因子：
6.1
通讯作者：
Poulter, W
中科院分区：
文献类型：
--
作者：
Cormican, L;O'Sullivan, S;Poulter, W
研究背景特应性哮喘患者与非特应性哮喘患者相比，其CD4(+)T细胞中干扰素-γ的产生受到抑制。目的探讨哮喘患者支气管壁T细胞亚群的凋亡水平是否与干扰素-γ的产生减少有关。方法对20例哮喘患者(10例特应性和10例非特应性)和8例非特应性非哮喘患者进行支气管镜检查。冰冻切片用免疫组织化学技术测定CD4/Fas+和CD4/Bcl2+细胞的相对数量。通过检测干扰素-γ(+)和白介素4(+)，结合TUNEL染色，检测Th1和Th2细胞的凋亡率。结果哮喘患者外周血中活化的CD4(+)T细胞比例明显升高，表现为表达人类白细胞抗原DR和CD25(+)。哮喘组CD_4~(+)细胞表达Bc l-2显著低于对照组(P=0.002)。哮喘组与非哮喘组CD4(+)Fas-L表达及细胞凋亡数目无明显差异。而IL-4(+)T细胞的凋亡率明显高于对照组(P=0.04)。结论哮喘炎症中Th1/Th2失衡可能是Th1亚群过早凋亡的结果。
Background Previous observations have established that IFN-gamma production is depressed in CD4(+) T cells from atopic asthmatics compared with non-asthmatics.Objective The aim of this study was to determine if decreased IFN-gamma production could be due to a dissociation between levels of apoptosis within the T cell subsets of the asthmatic bronchial wall.Methods Twenty asthmatics (10 atopic and 10 non-atopic) and eight non-atopic nonasthmatics underwent bronchoscopy. Cryostat sections of these biopsies were investigated using immunohistological techniques to determine the relative number of CD4/FAS+ and CD4/Bcl-2+ cells. Detection of IFN-gamma (+) and IL-4(+) was combined with TUNEL staining to determine the proportions of the Th1 and Th2 cells undergoing apoptosis.Results Experiments revealed raised proportions of activated CD4(+) T cells as assessed by expression of HLA-DR and CD25(+) expression in the asthmatic samples. Expression of Bcl-2 by the CD4(+) cell population was significantly reduced in the asthmatic compared with the control group (P = 0.002). There was mo significant difference in the expression of CD4(+) Fas-ligand or the number of CD4(+) undergoing apoptosis in the asthmatic and non-asthmatic groups. However, the IFN-gamma (+) (P = 0.04) but not IL-4(+) T cells in the asthmatic biopsies had significantly higher proportions of apoptotic cells compared with the control group.Conclusion The evidence supports the hypothesis that Th1/Th2 imbalance in asthmatic inflammation may be a result of premature apoptosis within the Th1 subset.