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在缓慢进展的原发性肺结核过程中小鼠肺组织中CD40、CD40L(CD154)、IL-12、TNF-α、IFN-γ和TGF-β1的原位表达

In situ expression of CD40, CD40L (CD154), IL-12, TNF-alpha, IFN-gamma and TGF-beta1 in murine lungs during slowly progressive primary tuberculosis.

作者信息

Mogga S J, Mustafa T, Sviland L, Nilsen R

机构信息

Centre for International Health, University of Bergen, Bergen, Norway.

出版信息

Scand J Immunol. 2003 Sep;58(3):327-34. doi: 10.1046/j.1365-3083.2003.01304.x.

DOI:10.1046/j.1365-3083.2003.01304.x
PMID:12950679
Abstract

The distribution and expression of CD40, its ligand CD40L (154) and related cytokines interleukin-12 (IL-12), tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and transforming growth factor-beta1 (TGF-beta1) were studied in the lungs of B6D2F1 hybrid mice during slowly progressive primary tuberculosis (TB) by immunohistochemistry. CD40 and CD40L are implicated in cell-mediated immunity (CMI) causing activation or apoptosis of infected cells. The phenomenon of apoptosis is associated with Mycobacterium tuberculosis survival. In this study, using frozen lung sections (n = 33), our results showed increased CD40, IL-12 and TGF-beta1 expression in macrophages with progression of disease. High percentages of mycobacterial antigens (M.Ags), CD40L and IFN-gamma expression were maintained throughout infection, and TNF-alpha-expressing cells were decreased. In lymphocytes, the percentage of IFN-gamma-positive cells was increased, but CD40L and IL-12 were maintained with the progression of disease. M.Ags, CD40 and CD40L were expressed in the same areas of the lesions. We conclude that changes in the expression of CD40-CD40L and cytokines associated with M. tuberculosis infection favour the hypothesis that M. tuberculosis causes resistance of host cells to apoptosis causing perpetuation of infection.

摘要

通过免疫组织化学方法,研究了B6D2F1杂交小鼠在缓慢进展性原发性肺结核(TB)期间肺组织中CD40及其配体CD40L(154)以及相关细胞因子白细胞介素-12(IL-12)、肿瘤坏死因子-α(TNF-α)、干扰素-γ(IFN-γ)和转化生长因子-β1(TGF-β1)的分布与表达。CD40和CD40L参与细胞介导的免疫(CMI),可导致受感染细胞的激活或凋亡。凋亡现象与结核分枝杆菌的存活有关。在本研究中,使用冰冻肺组织切片(n = 33),我们的结果显示,随着疾病进展,巨噬细胞中CD40、IL-12和TGF-β1的表达增加。在整个感染过程中,结核分枝杆菌抗原(M.Ags)、CD40L和IFN-γ的高表达持续存在,而表达TNF-α的细胞减少。在淋巴细胞中,IFN-γ阳性细胞的百分比增加,但随着疾病进展,CD40L和IL-12保持稳定。M.Ags、CD40和CD40L在病变的相同区域表达。我们得出结论,与结核分枝杆菌感染相关的CD40-CD40L和细胞因子表达的变化支持以下假说:结核分枝杆菌导致宿主细胞对凋亡产生抗性,从而使感染持续存在。

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