Admyre Charlotte, Bohle Barbara, Johansson Sara M, Focke-Tejkl Margarete, Valenta Rudolf, Scheynius Annika, Gabrielsson Susanne
Department of Medicine, Clinical Allergy Research Unit, Karolinska Institutet, Stockholm, Sweden.
J Allergy Clin Immunol. 2007 Dec;120(6):1418-24. doi: 10.1016/j.jaci.2007.06.040. Epub 2007 Sep 14.
Exosomes are vesicles of 30 to 100 nm produced by inward budding of endosomal compartments and are released by a range of different cell types. Exosomes from antigen-presenting cells carry immunorelevant molecules like MHC class I and II and costimulatory molecules and thus are suggested to have a role in immune modulation.
To investigate the role of antigen-presenting cell derived exosomes in allergen presentation and T-cell stimulation.
Exosomes were isolated from supernatants of B-cell lines derived from patients with birch pollen allergy. The exosomes were characterized with regard to the expression of surface molecules by flow cytometry. Moreover, exosomes were loaded with T-cell-activating peptides from the major birch allergen Bet v 1, and binding was tested with ELISA. Loaded exosomes were used for stimulation of Bet v 1-specific T-cell lines. Cell proliferation and cytokine production were assessed.
The exosomes had a phenotype typical of B cell-derived exosomes with expression of MHC, costimulatory molecules like CD86, tetraspanin proteins such as CD81, and CD19. Furthermore, B cell-derived exosomes bound Bet v 1-derived peptides and subsequently induced a dose-dependent T-cell proliferation. In addition to proliferation, T cells synthesized the cytokines IL-5 and IL-13 in response to peptide-loaded exosomes.
These results demonstrate for the first time that exosomes isolated from B cells can present allergen-derived peptides and thereby induce T-cell proliferation and T(H)2-like cytokine production.
Our data suggest that exosomes from B lymphocytes are an immunostimulatory factor in allergic immune responses.
外泌体是由内体区室向内出芽产生的30至100纳米的囊泡，由多种不同细胞类型释放。抗原呈递细胞来源的外泌体携带免疫相关分子，如MHC I类和II类分子以及共刺激分子，因此被认为在免疫调节中发挥作用。
研究抗原呈递细胞来源的外泌体在变应原呈递和T细胞刺激中的作用。
从桦树花粉过敏患者来源的B细胞系上清液中分离外泌体。通过流式细胞术对外泌体的表面分子表达进行表征。此外，将来自主要桦树变应原Bet v 1的T细胞激活肽加载到外泌体中，并用ELISA检测结合情况。用加载后的外泌体刺激Bet v 1特异性T细胞系。评估细胞增殖和细胞因子产生情况。
这些外泌体具有典型的B细胞来源外泌体的表型，表达MHC、共刺激分子如CD86、四跨膜蛋白如CD81和CD19。此外，B细胞来源的外泌体结合Bet v 1衍生的肽，并随后诱导剂量依赖性的T细胞增殖。除了增殖外，T细胞对加载肽的外泌体反应合成细胞因子IL-5和IL-13。
这些结果首次证明，从B细胞分离的外泌体可以呈递变应原衍生的肽，从而诱导T细胞增殖和产生类似Th2的细胞因子。
我们的数据表明，B淋巴细胞来源的外泌体是变应性免疫反应中的一种免疫刺激因子。
