The source of Mycobacterium tuberculosis-specific IFN-γ production in peripheral blood mononuclear cells of TB patients
The source of Mycobacterium tuberculosis-specific IFN-γ production in peripheral blood mononuclear cells of TB patients
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结核病患者外周血单核细胞中结核分枝杆菌特异性 IFN-γ 产生的来源
DOI：
10.1016/j.intimp.2016.01.012
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发表时间：
2016-03-01
影响因子：
5.6
通讯作者：
Sun, Ziyong
中科院分区：
文献类型：
--
作者：
Wang, Feng;Mao, Lie;Sun, Ziyong
结核分枝杆菌（Mtb）特异性IFN-γ分泌在抗结核（TB）免疫中起重要作用。在CD 4淋巴细胞计数低的HIV/TB合并感染患者中可以诱导Mtb特异性IFN-γ应答;这表明Mtb特异性IFN-γ产生的来源不限于CD 4（+）T淋巴细胞。目前，Mtb特异性IFN-γ产生的主要来源以及Mtb特异性IFN-γ产生细胞的功能和表型仍不清楚。根据常规测试和Mtb特异性IFN-γ ELISPOT测定招募了39名参与者（24名活动性TB患者，10名HIV/TB合并感染患者和5名健康志愿者）。采用多色流式细胞术研究Mtb特异性抗原刺激后外周血单个核细胞（PBMC）中细胞内IFN-γ的产生。我们的研究结果表明，CD 4（+），CD 8（+）T细胞和NK细胞都是结核病患者PBMC中产生Mtb特异性IFN-γ的主要来源。此外，CD 8（+）T细胞是HIV/TB共感染患者中Mtb特异性IFN-γ产生细胞的最高数量。虽然与健康对照相比，TB患者的NK细胞活性显著降低，但Mtb特异性抗原刺激诱导NK细胞活性显著增加。我们还表明，CD 45 RO是外周血中Mtb特异性IFN-γ产生T细胞的特征性标志物，但不是Mtb特异性IFN-γ产生NK细胞的特征性标志物。CD 11 a的高表达可能是Mtb特异性产生IFN-γ的NK细胞的特征性特征。本研究对结核病患者PBMC产生抗原特异性IFN-γ的来源提出了新的见解。(C)© 2016 Elsevier B. V.版权所有。
Mycobacterium tuberculosis (Mtb)-specific IFN-gamma secretion plays important roles in anti-tuberculosis (TB) immunity. Mtb-specific IFN-gamma response can be induced in HIV/TB co-infected patients with a low CD4 lymphocyte count; this suggests that the source of Mtb-specific IFN-gamma production is not limited in CD4(+) T lymphocytes. Currently, the major sources of Mtb-specific IFN-gamma production and the function and phenotype of Mtb-specific IFN-gamma-producing cells still remain unclear. Thirty-nine participants (24 active TB patients, 10 HIV/TB co-infected patients, and 5 healthy volunteers) were recruited according to conventional tests and Mtb-specific IFN-gamma ELISPOT assay. Multicolor flow cytometry was used to investigate the production of intracellular IFN-gamma in peripheral blood mononuclear cells (PBMCs) after Mtb-specific antigen stimulation. Our results showed that CD4(+), CD8(+) T cells and NK cells are all major sources of Mtb-specific IFN-gamma production in PBMCs of TB patients. Moreover, CD8(+) T cells are the highest number of Mtb-specific IFN-gamma-producing cells in HIV/TB co-infected patients. Although the activity of NK cells is significantly reduced in TB patients when compared with healthy controls, Mtb-specific antigen stimulation induces a significant increase in NK cell activity. We also showed that CD45RO is the characteristic marker of Mtb-specific IFN-gamma-producing T cells but not that of Mtb-specific IFN-gamma-producing NK cells in peripheral blood. High expression of CD11a may be the characteristic feature of Mtb-specific IFN-gamma-producing NK cells. This study put forward a new insight on the source of antigen-specific IFN-gamma-production in PBMCs of TB patients. (C) 2016 Elsevier B.V. All rights reserved.