Mycobacterium tuberculosis-specific CD8+ T cells are functionally and phenotypically different between latent infection and active disease.

Mycobacterium tuberculosis-specific CD8+ T cells are functionally and phenotypically different between latent infection and active disease.
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DOI:
10.1002/eji.201243262
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发表时间:
2013-06
影响因子:
5.4
通讯作者:
Harari A
Harari A
中科院分区:
医学3区
文献类型:
--
作者:
Rozot V;Vigano S;Mazza-Stalder J;Idrizi E;Day CL;Perreau M;Lazor-Blanchet C;Petruccioli E;Hanekom W;Goletti D;Bart PA;Nicod L;Pantaleo G;Harari A

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对结核分枝杆菌(Mtb)的保护性免疫仍知之甚少,Mtb特异性CD8 + T细胞的作用存在争议。在此,我们对326名潜伏性结核感染(LTBI)或活动性结核病(TB)患者的Mtb特异性CD8 + T细胞进行了广泛的表型和功能特征分析。在大多数(60%)结核病患者中检测到Mtb特异性CD8 + T细胞,而在少数(15%)LTBI受试者中也有检测到,但数量相似。LTBI受试者中的Mtb特异性CD8 + T细胞大多为TEMRA细胞(CD45RA + CCR7 - ),共表达2B4和CD160,而结核病患者中的Mtb特异性CD8 + T细胞大多为TEM细胞(CD45RA - CCR7 - ),表达2B4但缺乏PD - 1和CD160。两组的细胞因子谱没有显著差异。此外,Mtb特异性CD8 + T细胞表达低水平的穿孔素和颗粒溶素,但含有颗粒酶A和B。然而,体外扩增的Mtb特异性CD8 + T细胞表达穿孔素和颗粒溶素。最后,与肺结核患者相比,肺外结核患者中Mtb特异性CD8 + T细胞反应的检测频率较低。与肺结核患者相比,肺外结核患者中Mtb特异性CD8 + T细胞的增殖也更强。因此,Mtb感染的活动和临床表现与Mtb特异性CD8 + T细胞反应的不同特征相关。这些结果为Mtb与宿主免疫反应之间的相互作用提供了新的见解。
Protective immunity to Mycobacterium tuberculosis (Mtb) remains poorly understood and the role of Mtb-specific CD8+ T cells is controversial. Here we performed a broad phenotypic and functional characterization of Mtb-specific CD8+ T cells in 326 subjects with latent Mtb infection (LTBI) or active TB disease (TB). Mtb-specific CD8+ T cells were detected in most (60%) TB patients and few (15%) LTBI subjects but were of similar magnitude. Mtb-specific CD8+ T cells in LTBI subjects were mostly TEMRA cells (CD45RA+ CCR7− ), coexpressing 2B4 and CD160, and in TB patients were mostly TEM cells (CD45RA− CCR7− ), expressing 2B4 but lacking PD-1 and CD160. The cytokine profile was not significantly different in both groups. Furthermore, Mtb-specific CD8+ T cells expressed low levels of perforin and granulysin but contained granzymes A and B. However, in vitro-expanded Mtb-specific CD8+ T cells expressed perforin and granulysin. Finally, Mtb-specific CD8+ T-cell responses were less frequently detected in extrapulmonary TB compared with pulmonary TB patients. Mtb-specific CD8+ T-cell proliferation was also greater in patients with extrapulmonary compared with pulmonary TB. Thus, the activity of Mtb infection and clinical presentation are associated with distinct profiles of Mtb-specific CD8+ T-cell responses. These results provide new insights in the interaction between Mtb and the host immune response.
DOI: 10.1038/nm.2299
发表时间: 2011-03
期刊: Nature medicine
影响因子: 82.9
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影响因子: 15.3
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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
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发表时间: 2009-05-01
影响因子: 15.9
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