Kampmann B, Gaora P O, Snewin V A, Gares M P, Young D B, Levin M
Dept. of Paediatrics, Imperial College School of Medicine, St. Mary's Campus, London W2 1NY, United Kingdom.
J Infect Dis. 2000 Sep;182(3):895-901. doi: 10.1086/315766. Epub 2000 Aug 15.
A novel in vitro whole blood model was developed to study human antimycobacterial immunity. Recombinant reporter mycobacteria were used to enumerate the bacteria, and interactions between host immune cells and mycobacteria were studied using whole blood rather than cell fractions. The ability of healthy tuberculin-positive and tuberculin-negative individuals to restrict mycobacterial growth was compared. Growth of luminescent mycobacteria was significantly lower in blood samples of tuberculin-positive individuals than in blood samples of tuberculin-negative individuals (P=.005). Restricted mycobacterial growth was associated with significantly higher production of tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma (P=.01 and.004, respectively). Inhibition of the TNF-alpha and IFN-gamma response pathways by neutralizing monoclonal antibodies increased mycobacterial growth in whole blood. This model is the first functional assay in which individual variations in cell-mediated immunity are shown to correlate with differences in ability to control mycobacterial growth. It provides a new tool for studying human mycobactericidal mechanisms and, potentially, for the evaluation of improved vaccines.
为研究人类抗分枝杆菌免疫，开发了一种新型体外全血模型。使用重组报告分枝杆菌对细菌进行计数，并使用全血而非细胞组分来研究宿主免疫细胞与分枝杆菌之间的相互作用。比较了健康结核菌素阳性和结核菌素阴性个体限制分枝杆菌生长的能力。发光分枝杆菌在结核菌素阳性个体血样中的生长显著低于结核菌素阴性个体血样中的生长（P = 0.005）。分枝杆菌生长受限与肿瘤坏死因子（TNF）-α和干扰素（IFN）-γ的产生显著增加相关（分别为P = 0.01和0.004）。通过中和单克隆抗体抑制TNF-α和IFN-γ反应途径会增加全血中分枝杆菌的生长。该模型是首个功能性检测方法，其中细胞介导免疫的个体差异显示与控制分枝杆菌生长能力的差异相关。它为研究人类杀菌机制提供了新工具，并有可能用于评估改良疫苗。
