Analysis of Mycobacterium tuberculosis-specific CD8 T-cells in patients with active tuberculosis and in individuals with latent infection.
Analysis of Mycobacterium tuberculosis-specific CD8 T-cells in patients with active tuberculosis and in individuals with latent infection.
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DOI：
10.1371/journal.pone.0005528
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Ottenhoff TH
中科院分区：
文献类型：
--
作者：
Caccamo N;Guggino G;Meraviglia S;Gelsomino G;Di Carlo P;Titone L;Bocchino M;Galati D;Matarese A;Nouta J;Klein MR;Salerno A;Sanduzzi A;Dieli F;Ottenhoff TH
CD8 t细胞有助于结核分枝杆菌感染的控制，但对潜伏感染受试者和活动性结核病患者的CD8 t细胞反应的质量知之甚少。采用四聚体染色法检测了结核分枝杆菌6种不同蛋白表位的CD8 t细胞。细胞内细胞因子染色用于特异性产生IFN-γ和IL-2，并辅以抗原特异性CD8 t细胞的记忆标记表型。结核患者治疗前四聚体特异性CD8 t细胞的离体频率低于潜伏感染患者，但在治疗后4个月增加，与潜伏感染患者检测到的百分比相当。来自潜伏感染受试者的大多数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，而含有更高比例的细胞具有效应记忆和中枢记忆样表型，并且在治疗后没有显着改变。潜伏感染患者的CD8 t细胞显示IL-2+/IFN-γ+和IL-2 - /IFN-γ+ t细胞群共优势；有趣的是，在结核病患者中，只有IL-2+/IFN-γ+群体减少或缺失，这高度提示结核分枝杆菌特异性CD8 t细胞在活动性疾病期间的功能受限。这些结果表明结核分枝杆菌特异性CD8 t细胞表型和功能特征在控制感染的受试者（潜伏感染的受试者）和不控制感染的受试者（活动性疾病的患者）之间存在差异。
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-γ 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-γ+ and IL-2−/IFN-γ+ T-cell populations; interestingly, only the IL-2+/IFN-γ+ 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).
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影响因子：
4.4
作者：
Caccamo, Nadia;Meraviglia, Serena;Salerno, Alfredo
通讯作者：
Salerno, Alfredo
影响因子：
4.6
作者：
Hammond, AS;Klein, MR;Brookes, RH
通讯作者：
Brookes, RH
DOI：
10.1164/ajrccm.159.1.9801120
发表时间：
1999-01-01
影响因子：
24.7
作者：
Menzies, D
通讯作者：
Menzies, D
影响因子：
39.2
作者：
Menzies, Dick;Pai, Madhukar;Comstock, George
通讯作者：
Comstock, George
影响因子：
3.1
作者：
Klein, MR;Hammond, AS;McAdam, KPWJ
通讯作者：
McAdam, KPWJ