Sutherland Jayne S, Adetifa Ifedayo M, Hill Philip C, Adegbola Richard A, Ota Martin O C
Bacterial Diseases Programme, Medical Research Council Laboratories, Banjul, The Gambia.
Eur J Immunol. 2009 Mar;39(3):723-9. doi: 10.1002/eji.200838693.
Tuberculosis (TB) remains a global health problem. The solution involves development of an effective vaccine, but has been limited by incomplete understanding of what constitutes protective immunity during natural infection with Mycobacterium tuberculosis. In this study, M. tuberculosis-specific responses following an overnight whole-blood assay were assessed by intracellular cytokine staining and luminex, and compared between TB cases and exposed household contacts. TB cases had significantly higher levels of IFN-gamma(+)TNF-alpha(+)IL-2(+)CD4(+)T cells compared with contacts. TB cases also had a significantly higher proportion of cells single-positive for TNF-alpha, but lower proportion of cells producing IL-2 alone and these differences were seen for both CD4(+)and CD8(+) T cells. Cytokine profiles from culture supernatants were significantly biased toward a Th1 phenotype (IFN-gamma and IL-12(p40)) together with a complete abrogation of IL-17 secretion in TB cases. Our data indicate that despite a robust response to TB antigens in active TB disease, changes in the pattern of cytokine production between TB infection and disease clearly contribute to disease progression.
结核病仍然是一个全球性的健康问题。解决办法包括研发一种有效的疫苗，但由于对结核分枝杆菌自然感染期间构成保护性免疫的因素了解不全面，这一进程受到了限制。在本研究中，通过细胞内细胞因子染色和液相悬浮芯片技术评估过夜全血检测后的结核分枝杆菌特异性反应，并在结核病病例和有接触史的家庭接触者之间进行比较。与接触者相比，结核病病例中IFN-γ(+)TNF-α(+)IL-2(+)CD4(+)T细胞水平显著更高。结核病病例中TNF-α单阳性细胞的比例也显著更高，但单独产生IL-2的细胞比例更低，CD4(+)和CD8(+)T细胞均出现这些差异。结核病病例培养上清液中的细胞因子谱明显偏向Th1表型（IFN-γ和IL-12(p40)），同时IL-17分泌完全消失。我们的数据表明，尽管活动性结核病对结核抗原反应强烈，但结核感染和疾病之间细胞因子产生模式的变化显然促进了疾病进展。
