Direct exosome stimulation of peripheral human T cells detected by ELISPOT
Direct exosome stimulation of peripheral human T cells detected by ELISPOT
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DOI：
10.1002/eji.200535615
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发表时间：
2006-07-01
影响因子：
5.4
通讯作者：
Gabrielsson, Susanne
中科院分区：
文献类型：
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作者：
Admyre, Charlotte;Johansson, Sara M.;Gabrielsson, Susanne
来自APC的外泌体是纳米囊泡，可以诱导抗原特异性T细胞反应，目前在不同的临床环境中被探索作为治疗工具。外泌体体外刺激T细胞能力的研究大多是在T细胞杂交瘤、克隆或系上进行的。外泌体是否可以直接刺激T细胞或需要树突状细胞（DC）的存在是有争议的。我们可以在人的外周血中检测到外泌体诱导的抗原特异性CD8(+) T细胞反应。来自单核细胞衍生DC （MDDC）的外泌体装载了来自EBV、CMV和流感病毒的23种免疫原性肽的混合物，并添加到自体外周CD8(+) T细胞中。采用酶联免疫斑点法（ELISPOT）检测ifn - γ产生细胞。在不添加DC的情况下，mddc外泌体诱导CD8(+) T细胞产生ifn - γ。此外，我们检测到来自脂多糖成熟MDDC的外泌体比来自未成熟MDDC的外泌体具有更强的T细胞刺激能力。外泌体也可以诱导tnf - α的产生。这些结果首次表明，外泌体能够以抗原特异性的方式直接刺激人外周CD8(+) T细胞，ELISPOT是检测外泌体诱导的外周T细胞反应的合适方法。该系统可为开发外泌体作为治疗剂提供有用的工具。
Exosomes from APC are nano-vesicles that can induce antigen-specific T cell responses and are presently explored as therapeutic tools in different clinical settings. Investigations of the capacity of exosomes to stimulate T cells in vitro have mostly been performed on T cell hybridomas, clones or lines. Whether exosomes can stimulate T cells directly or need the presence of dendritic cells (DC) is debated. We could detect exosome-induced antigen-specific CD8(+) T cell responses in peripheral blood from humans. Exosomes from monocyte-derived DC (MDDC) were loaded with a mix of 23 immunogenic peptides from EBV, CMV and influenza virus, and added to autologous peripheral CD8(+) T cells. IFN-gamma-producing cells were detected by enzyme-linked immunospot assay (ELISPOT). MDDC-exosomes induced IFN-gamma production in CD8(+) T cells without addition of DC. The response was exosome dose dependent, and dependent on exosomal MHC class I. Furthermore, we detected an enhanced T cell stimulatory capacity by exosomes from lipopolysaccharide-matured MDDC compared to exosomes from immature MDDC. Exosomes could also induce TNF-alpha production. These results show, for the first time, that exosomes can directly stimulate human peripheral CD8(+) T cells in an antigen-specific manner and that ELISPOT is a suitable method for detecting exosome-induced peripheral T cell responses. This system may provide a useful tool when developing exosomes as therapeutic agents.