Feruglio S L, Kvale D, Dyrhol-Riise A M
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Norwegian Institute of Public Health, Oslo, Norway.
Scand J Immunol. 2017 Feb;85(2):138-146. doi: 10.1111/sji.12511.
Mycobacterium tuberculosis (Mtb) is particularly challenging for the immune system being an intracellular pathogen, and a variety of T cell subpopulations are activated by the host defence mechanism. In this study, we investigated T cell responses and regulation in active TB patients with drug-sensitive Mtb (N = 18) during 24 weeks of efficient anti-TB therapy. T cell activation, differentiation, regulatory T cell (Treg) subsets, Mtb-induced T cell proliferation and in vitro IL-10 and TGF-β modulation were analysed by flow cytometry at baseline and after 8 and 24 weeks of therapy, while soluble cytokines in culture supernatants were analysed by a 9-plex Luminex assay. Successful treatment resulted in significantly reduced co-expression of HLA-DR/CD38 and PD-1/CD38 on both CD4 and CD8 T cells, while the fraction of CD4 CD25 CD127 Tregs (P = 0.017) and CD4 CD25 CD127 CD147 Tregs (P = 0.029) showed significant transient increase at week 8. In vitro blockade of IL-10/TGF-β upon Mtb antigen stimulation significantly lowered the fraction of ESAT-6-specific CD4 CD25 CD127 Tregs at baseline (P = 0.047), while T cell proliferation and cytokine production were unaffected. Phenotypical and Mtb-specific T cell signatures may serve as markers of effective therapy, while the IL-10/TGF-β pathway could be a target for early inhibition to facilitate Mtb clearance. However, larger clinical studies are needed for verification before concluding.
结核分枝杆菌（Mtb）作为一种细胞内病原体，对免疫系统极具挑战性，宿主防御机制可激活多种T细胞亚群。在本研究中，我们调查了对药物敏感的Mtb活动性肺结核患者（N = 18）在24周有效抗结核治疗期间的T细胞反应和调节情况。在基线以及治疗8周和24周后，通过流式细胞术分析T细胞活化、分化、调节性T细胞（Treg）亚群、Mtb诱导的T细胞增殖以及体外IL-10和TGF-β调节情况，同时通过9联Luminex检测分析培养上清液中的可溶性细胞因子。成功治疗导致CD4和CD8 T细胞上HLA-DR/CD38和PD-1/CD38的共表达显著降低，而CD4 CD25 CD127 Tregs（P = 0.017）和CD4 CD25 CD127 CD147 Tregs（P = 0.029）的比例在第8周出现显著短暂增加。在Mtb抗原刺激后体外阻断IL-10/TGF-β可显著降低基线时ESAT-6特异性CD4 CD25 CD127 Tregs的比例（P = 0.047），而T细胞增殖和细胞因子产生未受影响。表型和Mtb特异性T细胞特征可作为有效治疗的标志物，而IL-10/TGF-β途径可能是早期抑制以促进Mtb清除的靶点。然而，在得出结论之前还需要更大规模的临床研究进行验证。
