Exosomes derived from M. Bovis BCG infected macrophages activate antigen-specific CD4+ and CD8+ T cells in vitro and in vivo.
Exosomes derived from M. Bovis BCG infected macrophages activate antigen-specific CD4+ and CD8+ T cells in vitro and in vivo.
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DOI：
10.1371/journal.pone.0002461
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发表时间：
2008-06-18
期刊：
影响因子：
3.7
通讯作者：
Schorey JS
中科院分区：
文献类型：
--
作者：
Giri PK;Schorey JS
对M的有效免疫应答需要CD 4+和CD 8 + T细胞的活化。肺结核感染。然而，受感染的巨噬细胞是不良的抗原呈递细胞，并且可能在空间上与募集的T细胞分离，从而限制肉芽肿内的抗原呈递。我们以前的研究表明，受感染的巨噬细胞从细胞中释放出小的膜结合囊泡，称为外泌体，其中含有分枝杆菌脂质成分，并表明这些外泌体可以刺激幼稚巨噬细胞的促炎反应。在本研究中，我们证明了外泌体刺激从分枝杆菌致敏小鼠中分离的CD 4+和CD 8+脾T细胞。虽然外来体含有MHC I和II以及共刺激分子，但T细胞的最大刺激需要先将外来体与抗原呈递细胞孵育。从M. bovis和M.结核感染的巨噬细胞也刺激小鼠骨髓来源的树突状细胞的活化和成熟。有趣的是，用从M. Bovis BCG感染的巨噬细胞诱导记忆性CD 4+和CD 8 + T细胞的产生。分离的T细胞在用BCG抗原再刺激后也产生IFN-γ。从感染的巨噬细胞中释放的外泌体可能克服了与分枝杆菌感染相关的抗原呈递缺陷，我们认为外泌体可能是一种有前途的分枝杆菌。结核病疫苗候选人。
Activation of both CD4+ and CD8+ T cells is required for an effective immune response to an M. tuberculosis infection. However, infected macrophages are poor antigen presenting cells and may be spatially separated from recruited T cells, thus limiting antigen presentation within a granuloma. Our previous studies showed that infected macrophages release from cells small membrane-bound vesicles called exosomes which contain mycobacterial lipid components and showed that these exosomes could stimulate a pro-inflammatory response in naïve macrophages. In the present study we demonstrate that exosomes stimulate both CD4+ and CD8+ splenic T cells isolated from mycobacteria-sensitized mice. Although the exosomes contain MHC I and II as well as costimulatory molecules, maximum stimulation of T cells required prior incubation of exosomes with antigen presenting cells. Exosomes isolated from M. bovis and M. tuberculosis infected macrophages also stimulated activation and maturation of mouse bone marrow-derived dendritic cells. Interestingly, intranasal administration of mice with exosomes isolated from M. bovis BCG infected macrophages induce the generation of memory CD4+ and CD8+ T cells. The isolated T cells also produced IFN-γ upon restimulation with BCG antigens. The release of exosomes from infected macrophages may overcome some of the defects in antigen presentation associated with mycobacterial infections and we suggest that exosomes may be a promising M. tuberculosis vaccine candidate.
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影响因子：
4.5
作者：
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通讯作者：
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DOI：
10.1073/pnas.84.12.4205
发表时间：
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DOI：
10.1084/jem.20052545
发表时间：
2006-07-10
期刊：
The Journal of experimental medicine
影响因子：
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作者：
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通讯作者：
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