潜伏性结核分枝杆菌感染特异性T细胞抗原的鉴定。

Identification of T-cell antigens specific for latent mycobacterium tuberculosis infection.

作者信息

Schuck Sebastian D, Mueller Henrik, Kunitz Frank, Neher Albert, Hoffmann Harald, Franken Kees L C M, Repsilber Dirk, Ottenhoff Tom H M, Kaufmann Stefan H E, Jacobsen Marc

机构信息

Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.

出版信息

PLoS One. 2009;4(5):e5590. doi: 10.1371/journal.pone.0005590. Epub 2009 May 18.

BACKGROUND

T-cell responses against dormancy-, resuscitation-, and reactivation-associated antigens of Mycobacterium tuberculosis are candidate biomarkers of latent infection in humans.

METHODOLOGY/PRINCIPAL FINDINGS: We established an assay based on two rounds of in vitro restimulation and intracellular cytokine analysis that detects T-cell responses to antigens expressed during latent M. tuberculosis infection. Comparison between active pulmonary tuberculosis (TB) patients and healthy latently M. tuberculosis-infected donors (LTBI) revealed significantly higher T-cell responses against 7 of 35 tested M. tuberculosis latency-associated antigens in LTBI. Notably, T cells specific for Rv3407 were exclusively detected in LTBI but not in TB patients. The T-cell IFNgamma response against Rv3407 in individual donors was the most influential factor in discrimination analysis that classified TB patients and LTBI with 83% accuracy using cross-validation. Rv3407 peptide pool stimulations revealed distinct candidate epitopes in four LTBI.

CONCLUSIONS

Our findings further support the hypothesis that the latency-associated antigens can be exploited as biomarkers for LTBI.

背景

针对结核分枝杆菌休眠、复苏和再激活相关抗原的T细胞反应是人类潜伏感染的候选生物标志物。

方法/主要发现：我们建立了一种基于两轮体外再刺激和细胞内细胞因子分析的检测方法，用于检测对潜伏性结核分枝杆菌感染期间表达的抗原的T细胞反应。活动性肺结核（TB）患者与健康的潜伏性结核分枝杆菌感染供体（LTBI）之间的比较显示，LTBI中针对35种测试的结核分枝杆菌潜伏相关抗原中的7种的T细胞反应明显更高。值得注意的是，仅在LTBI中检测到针对Rv3407的特异性T细胞，而在TB患者中未检测到。个体供体中针对Rv3407的T细胞IFNγ反应是判别分析中最具影响力的因素，使用交叉验证对TB患者和LTBI进行分类的准确率为83%。Rv3407肽库刺激在四名LTBI中揭示了不同的候选表位。