Patients with tuberculosis disease have Mycobacterium tuberculosis-specific CD8 T cells with a pro-apoptotic phenotype and impaired proliferative capacity, which is not restored following treatment.
Patients with tuberculosis disease have Mycobacterium tuberculosis-specific CD8 T cells with a pro-apoptotic phenotype and impaired proliferative capacity, which is not restored following treatment.
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DOI：
10.1371/journal.pone.0094949
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Hanekom WA
中科院分区：
文献类型：
--
作者：
Day CL;Moshi ND;Abrahams DA;van Rooyen M;O'rie T;de Kock M;Hanekom WA
CD8 T细胞在控制慢性病毒感染中起着关键作用；然而，这些细胞在控制持续性细菌感染（如结核分枝杆菌（Mtb）引起的感染）中的作用尚不明确。我们评估了肺结核（TB）患者在治疗前后以及潜伏性结核分枝杆菌感染（LTBI）的健康人针对免疫优势Mtb抗原CFP - 10和ESAT - 6的特异性CD8 T细胞的表型和功能能力。在肺结核患者中，CFP - 10/ESAT - 6特异性IFN - γ⁺ CD8 T细胞具有活化的、促凋亡的表型，与LTBI相比，其Bcl - 2和CD127表达较低，Ki67、CD57和CD95表达较高。当可检测到CFP - 10/ESAT - 6特异性IFN - γ⁺ CD8 T细胞时，这些标志物的不同组合的表达对于区分肺结核和LTBI具有高度的敏感性和特异性。疾病的成功治疗导致这些标志物发生变化，但CFP - 10/ESAT - 6特异性CD8或CD4记忆T细胞的增殖能力未恢复。这些数据表明，活动性肺结核疾病中高的分枝杆菌负荷与活化的、寿命短的CFP - 10/ESAT - 6特异性CD8 T细胞相关，其功能能力受损且在治疗后未恢复。相比之下，LTBI与寿命长的CFP - 10/ESAT - 6特异性记忆CD8 T细胞的保留相关，这些细胞维持高的Bcl - 2表达并且可能易于增殖。
CD8 T cells play a critical role in control of chronic viral infections; however, the role of these cells in containing persistent bacterial infections, such as those caused by Mycobacterium tuberculosis (Mtb), is less clear. We assessed the phenotype and functional capacity of CD8 T cells specific for the immunodominant Mtb antigens CFP-10 and ESAT-6, in patients with pulmonary tuberculosis (TB) disease, before and after treatment, and in healthy persons with latent Mtb infection (LTBI). In patients with TB disease, CFP-10/ESAT-6-specific IFN-γ+ CD8 T cells had an activated, pro-apoptotic phenotype, with lower Bcl-2 and CD127 expression, and higher Ki67, CD57, and CD95 expression, than in LTBI. When CFP-10/ESAT-6-specific IFN-γ+ CD8 T cells were detectable, expression of distinct combinations of these markers was highly sensitive and specific for differentiating TB disease from LTBI. Successful treatment of disease resulted in changes of these markers, but not in restoration of CFP-10/ESAT-6-specific CD8 or CD4 memory T cell proliferative capacity. These data suggest that high mycobacterial load in active TB disease is associated with activated, short-lived CFP-10/ESAT-6-specific CD8 T cells with impaired functional capacity that is not restored following treatment. By contrast, LTBI is associated with preservation of long-lived CFP-10/ESAT-6-specific memory CD8 T cells that maintain high Bcl-2 expression and which may readily proliferate.
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影响因子：
82.9
作者：
Harari A;Rozot V;Bellutti Enders F;Perreau M;Stalder JM;Nicod LP;Cavassini M;Calandra T;Blanchet CL;Jaton K;Faouzi M;Day CL;Hanekom WA;Bart PA;Pantaleo G
通讯作者：
Pantaleo G
影响因子：
3.7
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
通讯作者：
Ottenhoff TH
DOI：
10.1084/jem.175.4.1111
发表时间：
1992-04-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chan J;Xing Y;Magliozzo RS;Bloom BR
通讯作者：
Bloom BR
DOI：
10.4049/jimmunol.1101122
发表时间：
2011-09-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Day CL;Abrahams DA;Lerumo L;Janse van Rensburg E;Stone L;O'rie T;Pienaar B;de Kock M;Kaplan G;Mahomed H;Dheda K;Hanekom WA
通讯作者：
Hanekom WA
影响因子：
4.4
作者：
Caccamo, Nadia;Meraviglia, Serena;Salerno, Alfredo
通讯作者：
Salerno, Alfredo