Regulatory T cells induced by Mycobacterium chelonae sensitization influence murine responses to bacille Calmette-Guerin
Regulatory T cells induced by Mycobacterium chelonae sensitization influence murine responses to bacille Calmette-Guerin
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DOI：
10.1189/jlb.0809582
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发表时间：
2010-12-01
影响因子：
5.5
通讯作者：
Seah, Geok Teng
中科院分区：
文献类型：
--
作者：
Ho, Peiying;Wei, Xing;Seah, Geok Teng
活牛分枝杆菌BCG作为结核病疫苗的效力在全球范围内差异很大。卡介苗接种前对环境分枝杆菌的差异致敏可能引发导致这种变异的免疫效应，但这种现象所涉及的精确免疫机制和细胞类型尚不清楚。我们假设接种前对环境分枝杆菌的致敏诱导了抑制对BCG反应的分枝杆菌特异性T细胞。这通过在用热灭活的CHE腹膜内免疫引发BALB/c小鼠后测试Treg应答来研究。与未致敏小鼠相比，这些小鼠在鼻内给予活BCG之前和之后产生更高水平的IL-10，并且在BCG后具有更少的肺部炎症细胞。在CHE致敏小鼠中，表达Foxp 3的脾CD 4（+）CD 25（+）细胞在总淋巴细胞中的百分比没有显著升高，但这些细胞在共培养时限制了CD 4（+）CD 25（-）效应细胞的非特异性增殖，并且在响应BCG抗原刺激时促进了比来自非致敏小鼠的CD 4（+）CD 25（-）细胞更高的CD 103和Foxp 3表达水平。在过继转移实验中，接受来自CHE致敏小鼠的CD 4（+）CD 25（-）细胞，然后鼻内给予活BCG的未处理WT小鼠的肺IL-10水平显著升高，肺IL-2产生细胞的频率降低，BAL中淋巴细胞数量减少。因此，CHE致敏诱导的CD 4（+）CD 25（-）T细胞在体外和体内对BCG应答具有功能性抑制活性。因此，Treg诱导可能是环境分枝杆菌引发如何调节宿主对BCG疫苗应答的一种机制。J. Leukoc. 88：1073-1080; 2010.
The efficacy of live Mycobacterium bovis BCG as a tuberculosis vaccine is highly varied globally. Differential sensitization to environmental mycobacteria prior to BCG vaccination may prime immune effects leading to this variation, but the precise immune mechanisms and cell types involved in this phenomenon are unknown. We hypothesized that pre-vaccination sensitization to environmental mycobacteria induces mycobacterium-specific Tregs that suppress responses to BCG. This was investigated by testing Treg responses following priming of BALB/c mice by i.p. immunization with heat-killed CHE. Such mice produced higher levels of IL-10 before and after intranasal, live BCG administration and had fewer lung inflammatory cells post-BCG, relative to nonsensitized mice. In CHE-sensitized mice, the percentage of splenic CD4(+)CD25(+) cells expressing Foxp3 amongst total lymphocytes was not elevated significantly, but these cells limited nonspecific proliferation of CD4(+)CD25(-) effector cells upon coculture and promoted higher expression levels of CD103 and Foxp3 in response to BCG antigen stimulation than CD4(+)CD25(-) cells from nonsensitized mice. In adoptive transfer experiments, naive, WT mice receiving CD4(+)CD25(-) cells from CHE-sensitized mice and then given live BCG intranasally had significantly elevated lung IL-10 levels, reduced frequencies of lung IL-2-producing cells, and lower lymphocyte numbers in the BAL. Therefore, CHE sensitization induced CD4(+)CD25(-) Tregs with functional, suppressive activity on BCG responses in vitro and in vivo. Treg induction could therefore be one mechanism underlying how environmental mycobacteria priming modulates host responses to the BCG vaccine. J. Leukoc. Biol. 88: 1073-1080; 2010.