Caccamo Nadia, Guggino Giuliana, Meraviglia Serena, Gelsomino Giuseppe, Di Carlo Paola, Titone Lucina, Bocchino Marialuisa, Galati Domenico, Matarese Alessandro, Nouta Jan, Klein Michel R, Salerno Alfredo, Sanduzzi Alessandro, Dieli Francesco, Ottenhoff Tom H M
Dipartimento di Biopatologia e Metodologie Biomediche, Università di Palermo, Palermo, Italy.
PLoS One. 2009;4(5):e5528. doi: 10.1371/journal.pone.0005528. Epub 2009 May 13.
CD8 T-cells contribute to control of Mycobacterium tuberculosis infection, but little is known about the quality of the CD8 T-cell response in subjects with latent infection and in patients with active tuberculosis disease. CD8 T-cells recognizing epitopes from 6 different proteins of Mycobacterium tuberculosis were detected by tetramer staining. Intracellular cytokines staining for specific production of IFN-gamma and IL-2 was performed, complemented by phenotyping of memory markers on antigen-specific CD8 T-cells. The ex-vivo frequencies of tetramer-specific CD8 T-cells in tuberculous patients before therapy were lower than in subjects with latent infection, but increased at four months after therapy to comparable percentages detected in subjects with latent infection. The majority of CD8 T-cells from subjects with latent infection expressed a terminally-differentiated phenotype (CD45RA+CCR7(-)). In contrast, tuberculous patients had only 35% of antigen-specific CD8 T-cells expressing this phenotype, while containing higher proportions of cells with an effector memory- and a central memory-like phenotype, and which did not change significantly after therapy. CD8 T-cells from subjects with latent infection showed a codominance of IL-2+/IFN-gamma+ and IL-2(-)/IFN-gamma+ T-cell populations; interestingly, only the IL-2+/IFN-gamma+ population was reduced or absent in tuberculous patients, highly suggestive of a restricted functional profile of Mycobacterium tuberculosis-specific CD8 T-cells during active disease. These results suggest distinct Mycobacterium tuberculosis specific CD8 T-cell phenotypic and functional signatures between subjects which control infection (subjects with latent infection) and those who do not (patients with active disease).
CD8 T细胞有助于控制结核分枝杆菌感染，但对于潜伏感染的个体和活动性结核病患者中CD8 T细胞反应的质量了解甚少。通过四聚体染色检测识别结核分枝杆菌6种不同蛋白表位的CD8 T细胞。进行细胞内细胞因子染色以检测IFN-γ和IL-2的特异性产生，并通过对抗原特异性CD8 T细胞上记忆标志物的表型分析进行补充。结核患者治疗前四聚体特异性CD8 T细胞的体外频率低于潜伏感染个体，但在治疗4个月后增加到与潜伏感染个体中检测到的百分比相当。潜伏感染个体中的大多数CD8 T细胞表达终末分化表型（CD45RA+CCR7(-)）。相比之下，结核病患者只有35%的抗原特异性CD8 T细胞表达这种表型，同时含有较高比例的具有效应记忆样和中央记忆样表型的细胞，且治疗后没有显著变化。潜伏感染个体的CD8 T细胞显示IL-2+/IFN-γ+和IL-2(-)/IFN-γ+ T细胞群体的共显性；有趣的是，结核病患者中只有IL-2+/IFN-γ+群体减少或缺失，这强烈提示在活动性疾病期间结核分枝杆菌特异性CD8 T细胞的功能谱受限。这些结果表明，在控制感染的个体（潜伏感染个体）和未控制感染的个体（活动性疾病患者）之间，结核分枝杆菌特异性CD8 T细胞具有不同的表型和功能特征。
