In situ production of gamma interferon, interleukin-4, and tumor necrosis factor alpha mRNA in human lung tuberculous granulomas
In situ production of gamma interferon, interleukin-4, and tumor necrosis factor alpha mRNA in human lung tuberculous granulomas
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DOI：
10.1128/iai.68.5.2827-2836.2000
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发表时间：
2000-05-01
影响因子：
3.1
通讯作者：
Lukey, PT
中科院分区：
文献类型：
--
作者：
Fenhalls, G;Wong, A;Lukey, PT
采用非放射性原位杂交法检测了5例成人肺结核咯血手术标本中肿瘤坏死因子-α(TNF-α)、干扰素(IFN-γ)和白介素4(IL-4)的基因表达。所有患者均产生肿瘤坏死因子-αmRNA。3例干扰素-γ和IL-4m RNA均阳性，2例干扰素-γ阳性但不表达IL-4m RNA，两者均阳性者肉芽肿呈异质性；这些患者的肉芽肿有干扰素-γ而不是IL-4mRNA，以及两种细胞因子mRNAs阳性的肉芽肿，这些肉芽肿中没有干酪化的证据，细胞因子模式可能代表了肉芽肿的演变过程，然而，在那些表现为干酪样坏死的肉芽肿中，几乎没有观察到干扰素-γ或IL-4mRNA，这意味着肉芽肿的进展伴随着T细胞反应的下调。同时存在干扰素-γ和IL-4m RNA的患者，肿瘤坏死因子-αm RNA的表达最高。肉芽肿内CD68阳性的巨噬细胞样细胞群产生肿瘤坏死因子-α、干扰素-γ和白介素4的mRNA。这表明，结核肉芽肿内的巨噬细胞可能不依赖T细胞细胞因子来调节其功能，但可能能够调节自身和周围T细胞的激活状态。这些发现对结核病患者的免疫治疗具有一定的指导意义。
Human tuberculous granulomas from five adults undergoing surgery for hemoptysis were analyzed by nonradioactive in situ hybridization for tumor necrosis factor alpha (TNF-alpha), gamma interferon (IFN-gamma), and interleukin-4 (IL-4) gene expression. All of the patients produced TNF-alpha mRNA. Three patients stained positive for both IFN-gamma and IL-4 mRNA; the other two stained positive for IFN-gamma but not IL-4 mRNA, Heterogeneity between the granulomas was observed in those patients staining positive for both IFN-gamma and IL-4 mRNA; these patients exhibited granulomas having IFN-gamma and not IL-4 mRNA as well as granulomas positive for both cytokine mRNAs, There was no evidence of caseation in these granulomas, and the cytokine patterns may represent events in the evolution of the granuloma, However, in those granulomas exhibiting caseous necrosis, very little IFN-gamma or IL-4 mRNA was observed, implying that progression of the granuloma is accompanied by a down regulation of T-cell responses. TNF-alpha mRNA expression was highest in patients with both IFN-gamma and IL-4 mRNA. Populations of CD68 positive macrophage-like cells within the granulomas produce mRNA for TNF-alpha, IFN-gamma, and IL-4. This implies that macrophages within the tuberculous granuloma may not be dependent on T-cell cytokines for modulation of their function but may be able to regulate their own activation state and that of the surrounding T cells. These findings have implications on the delivery of immunotherapies to patients with tuberculosis.