Mycobacterium tuberculosis-specific CD4+, IFNγ+, and TNFα+ multifunctional memory T cells coexpress GM-CSF
Mycobacterium tuberculosis-specific CD4+, IFNγ+, and TNFα+ multifunctional memory T cells coexpress GM-CSF
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DOI：
10.1016/j.cyto.2008.05.002
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发表时间：
2008-08-01
期刊：
影响因子：
3.8
通讯作者：
Jacobsen, Marc
中科院分区：
文献类型：
--
作者：
Mueller, Henrik;Detjen, Anne K.;Jacobsen, Marc
同时表达几种细胞因子的多功能T细胞被认为在抵御不同感染方面发挥着关键作用。为了研究结核分枝杆菌感染中与疾病和保护相关的T细胞因子模式，我们测定了经短期体外再刺激后，结核病(TB)儿童和健康隐匿性结核感染儿童(LTBI)T细胞亚群中干扰素-γ、IL-2、肿瘤坏死因子-α和GM-CSF的表达。在抗原特异性再刺激后，我们发现CD4(+)效应记忆T细胞(T-EM)是所有被测细胞因子的主要来源。结核患儿的TM在Mtb再刺激后表达了更高比例的干扰素-γ、肿瘤坏死因子-α和IL-2，而GM-CSF在两组研究中没有检测到差异。GM-CSF的分泌强烈依赖于抗原特异性刺激。多种细胞因子模式分析显示，大多数GM-CSF阳性的结核分枝杆菌特异性记忆T细胞共表达干扰素-γ和肿瘤坏死因子-α，具有多功能T细胞的特征。我们得出的结论是，活动性肺结核患儿较LTBI患儿具有更高比例的干扰素-γ、肿瘤坏死因子-α和/或IL-2阳性的透射电子显微镜，而GM-CSF共表达揭示了活动性肺结核患儿的CD4(+)记忆T细胞中有一个新的亚群没有增加。(C)2008爱思唯尔有限公司。保留所有权利。
Multifunctional T cells expressing several cytokines in parallel are thought to play a crucial role in protection against different infections. To characterize T cell cytokine patterns associated with disease and protection in Mycobacterium tuberculosis infection we determined the expression of IFN gamma, IL-2, TNF alpha, and GM-CSF in T cell subpopulations from children with tuberculosis (TB) and healthy latently M. tuberculosis-infected children (LTBI) after short-term in vitro restimulation. We identified CD4(+) effector memory T cells (T-EM) as the major source of all measured cytokines after antigen-specific restimulation. TEM from children with TB expressed higher proportions of IFN gamma, TNF alpha, and IL-2 after Mtb restimulation while no differences were detected for GM-CSF between both study groups. GM-CSF secretion strongly depended on antigen-specific stimulation. Analyses of multiple cytokine patterns revealed that the majority of GM-CSF-positive M. tuberculosis-specific memory T cells coexpressed IFN gamma and TNF alpha therefore showing a characteristic feature of multifunctional T cells. We conclude that children with active TB possess higher proportions of IFN gamma-, TNF alpha-, and/or IL-2-positive TEM than children with LTBI while GM-CSF coexpression reveals a novel subpopulation within CD4(+) memory T cells not increased in children with active TB. (c) 2008 Elsevier Ltd. All rights reserved.