Feruglio S L, Tonby K, Kvale D, Dyrhol-Riise A M
Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Norwegian Institute of Public Health, Oslo, Norway.
Clin Exp Immunol. 2015 Mar;179(3):454-65. doi: 10.1111/cei.12468.
Biomarkers that can identify tuberculosis (TB) disease and serve as markers for efficient therapy are requested. We have studied T cell cytokine production [interferon (IFN)-γ, interleukin (IL)-2, tumour necrosis factor (TNF)-α] and degranulation (CD107a) as well as subsets of CD4(+) T regulatory cells (Tregs ) after in-vitro Mycobacterium tuberculosis (Mtb) antigen stimulation [early secretory antigenic target (ESAT)-6, culture filtrate protein (CFP)-10, antigen 85 (Ag85)] in 32 patients with active tuberculosis (TB) disease throughout 24 weeks of effective TB treatment. A significant decline in the fraction of Mtb-specific total IFN-γ and single IFN-γ-producing T cells was already observed after 2 weeks of treatment, whereas the pool of single IL-2(+) cells increased over time for both CD4(+) and CD8(+) T cells. The Treg subsets CD25(high) CD127(low) , CD25(high) CD147(++) and CD25(high) CD127(low) CD161(+) expanded significantly after Mtb antigen stimulation in vitro at all time-points, whereas the CD25(high) CD127(low) CD39(+) Tregs remained unchanged. The fraction of CD25(high) CD127(low) Tregs increased after 8 weeks of treatment. Thus, we revealed an opposing shift of Tregs and intracellular cytokine production during treatment. This may indicate that functional signatures of the CD4(+) and CD8(+) T cells can serve as immunological correlates of early curative host responses. Whether such signatures can be used as biomarkers in monitoring and follow-up of TB treatment needs to be explored further.
需要能够识别结核病（TB）并作为有效治疗标志物的生物标志物。我们研究了32例活动性结核病患者在24周有效抗结核治疗期间，体外结核分枝杆菌（Mtb）抗原刺激[早期分泌性抗原靶标（ESAT）-6、培养滤液蛋白（CFP）-10、抗原85（Ag85）]后T细胞细胞因子的产生[干扰素（IFN）-γ、白细胞介素（IL）-2、肿瘤坏死因子（TNF）-α]、脱颗粒（CD107a）以及CD4(+)调节性T细胞（Tregs）亚群。治疗2周后，已观察到Mtb特异性总IFN-γ和单个产生IFN-γ的T细胞比例显著下降，而对于CD4(+)和CD8(+) T细胞，单个IL-2(+)细胞池随时间增加。在所有时间点，体外Mtb抗原刺激后，Treg亚群CD25(高)CD127(低)、CD25(高)CD147(++)和CD25(高)CD127(低)CD161(+)显著扩增，而CD25(高)CD127(低)CD39(+) Tregs保持不变。治疗8周后，CD25(高)CD127(低) Tregs比例增加。因此，我们揭示了治疗期间Tregs和细胞内细胞因子产生的相反变化。这可能表明CD4(+)和CD8(+) T细胞的功能特征可作为宿主早期治愈反应的免疫学相关指标。此类特征是否可作为结核病治疗监测和随访中的生物标志物，有待进一步探索。
