Coppieters Ken, Barral Ana María, Juedes Amy, Wolfe Tom, Rodrigo Evelyn, Théry Clotilde, Amigorena Sebastian, von Herrath Matthias G
Immune Regulation Laboratory DI-3, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
J Immunol. 2009 Feb 15;182(4):2213-20. doi: 10.4049/jimmunol.0802578.
Exosomes are small membrane vesicles of endocytic origin that are secreted by most cells in culture, but are also present in serum. They contain a wide array of protein ligands on their surface, which has led to the hypothesis that they might mediate intercellular communication. Indeed, data support that exosomes can transfer Ags to dendritic cells (DC), and, interestingly, that these DC can subsequently induce T cell priming or tolerance. We have investigated whether this concept can be expanded to antiviral immunity. We isolated exosomes from supernatant of cultured bone marrow-derived DC (BMDC) that were infected with lymphocytic choriomeningitis virus (LCMV) or loaded with an immunodominant LCMV peptide, and characterized them by flow cytometry upon binding to beads. We then incubated the exosome preparations with BMDC and looked at their potential to activate LCMV gp33-specific naive and memory CD8 T cells. We found that exosomes do not significantly contribute to CD8 T cell cross-priming in vitro. Additionally, exosomes derived from in vitro-infected BMDC did not exhibit significant in vivo priming activity, as evidenced by the lack of protection following exosome vaccination. Thus, DC-derived exosomes do not appear to contribute significantly to CTL priming during acute LCMV infection.
外泌体是起源于内吞作用的小膜泡，由培养中的大多数细胞分泌，但也存在于血清中。它们表面含有多种蛋白质配体，这引发了一种假说，即它们可能介导细胞间通讯。事实上，有数据支持外泌体可以将抗原转移至树突状细胞（DC），有趣的是，这些DC随后能够诱导T细胞致敏或耐受。我们研究了这一概念是否能够扩展至抗病毒免疫。我们从感染淋巴细胞性脉络丛脑膜炎病毒（LCMV）或负载免疫显性LCMV肽的培养骨髓来源DC（BMDC）的上清液中分离出外泌体，并在其与珠子结合后通过流式细胞术对其进行表征。然后，我们将外泌体制剂与BMDC一起孵育，并观察它们激活LCMV gp33特异性初始和记忆CD8 T细胞的潜力。我们发现外泌体在体外对CD8 T细胞交叉致敏没有显著贡献。此外，源自体外感染BMDC的外泌体在体内没有表现出显著的致敏活性，外泌体疫苗接种后缺乏保护作用就证明了这一点。因此，在急性LCMV感染期间，DC来源的外泌体似乎对CTL致敏没有显著贡献。
