Exosomes secreted from monocyte-derived dendritic cells support in vitro naive CD4+ T cell survival through NF-κB activation
Exosomes secreted from monocyte-derived dendritic cells support in vitro naive CD4+ T cell survival through NF-κB activation
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DOI：
10.1016/j.cellimm.2004.11.002
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发表时间：
2004-09-01
影响因子：
4.3
通讯作者：
Katano, M
中科院分区：
文献类型：
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作者：
Matsumoto, K;Morisaki, T;Katano, M
我们研究了从人单核细胞来源的树突状细胞（Mo-DC）分泌的外泌体对体外幼稚CD 4（+）T细胞存活的影响，所述树突状细胞由PBMCs响应于GM-CSF和IL-4处理而产生。用抗HLA-DP、-DQ、-DR包被的顺磁珠纯化从Mo-DC的培养上清液分离的外来体（> 90%纯度）。纯化的外泌体在体外延长了初始CD 4（+）T细胞（纯度> 98%）的存活。用抗HLA-DR的中和mAb治疗显著降低了纯化的外泌体对CD 4（+）T细胞存活的支持作用。外来体增加了初始CD 4（+）T细胞中NF-κ B的核转位，并且NF-κ B活化被抗HLA-DR mAb或NF-κ B抑制剂吡咯烷二硫代氨基甲酸酯（PDTC）显著抑制。此外，PDTC抑制外来体对初始CD 4（+）T细胞存活的影响。因此，Mo-DC分泌的外泌体似乎通过由HLA-DR和TCR相互作用诱导的NF-κ B活化来支持初始CD 4（+）T细胞存活。(c)2004年爱思唯尔公司All rights reserved.
We investigated the effect of exosomes secreted from human monocyte-derived dendritic cells (Mo-DCs), which are generated from PBMCs in response to treatment with GM-CSF and IL-4, on naive CD4(+) T cell survival in vitro. Exosomes isolated from culture supernatants of Mo-DCs (> 90% purity) were purified with anti-HLA-DP, -DQ, -DR-coated paramagnetic beads. Purified exosomes prolonged the survival of naive CD4(+) T cells (> 98% purity) in vitro. Treatment with neutralizing mAb against HLA-DR significantly decreased the supportive effect of purified exosomes on CD4(+) T cell survival. Exosomes increased nuclear translocation of NF-kappa B in naive CD4(+) T cells, and NF-kappa B activation was significantly suppressed by anti-HLA-DR mAb or NF-kappa B inhibitor pyrrolidine dithiocarbamate (PDTC). In addition, PDTC inhibited the effect of exosomes on naive CD4(+) T cell survival. Thus, exosomes secreted by Mo-DCs appear to support naive CD4(+) T cell survival via NF-kappa B activation induced by interaction of HLA-DR and TCRs. (c) 2004 Elsevier Inc. All rights reserved.