Antigen-loaded exosomes alone induce Th1-type memory through a B cell-dependent mechanism
Antigen-loaded exosomes alone induce Th1-type memory through a B cell-dependent mechanism
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DOI：
10.1182/blood-2008-04-153536
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发表时间：
2009-03-19
期刊：
影响因子：
20.3
通讯作者：
Gabrielsson, Susanne
中科院分区：
文献类型：
--
作者：
Qazi, Khaleda Rahman;Gehrmann, Ulf;Gabrielsson, Susanne
外切体是含有对抗原呈递很重要的蛋白质的纳米囊泡。我们比较了不同负载的外切体，直接负载OVA(323-339)肽(Pep-Exo)或来自OVA冲击的DC的Exosome(OVA-Exo)在体外和体内诱导特异性T细胞增殖的能力。Pep-Exo和OVA-Exo在体外均能诱导特异性的转基因T细胞增殖，但Pep-Exo的效果更好。相比之下，只有OVA-Exo在体内诱导了特异性T细胞反应，突显了间接负载策略在临床应用中的重要性。全卵联合给药克服了Pep-Exo的无反应性，但与OVA-Exo相比，反应仍较低。同时，我们发现OVA-Exo不仅增强了特异性T细胞反应，而且即使在没有完整OVA的情况下也能引起Th1型转变和抗体反应。我们检测了脾细胞产生的IgG2a和干扰素-γ，显示了外体为B细胞激活提供抗原的能力。此外，我们发现B细胞是胞外T细胞刺激所必需的，因为Bruton酪氨酸激酶缺陷小鼠在OVA-Exo免疫后表现出B细胞和T细胞反应被破坏。这些发现表明，外切体是有效的免疫调节器，并与疫苗佐剂的设计和调节免疫反应的治疗干预策略有关。(血。2009；113：2673-2683)
Exosomes are nanovesicles harboring proteins important for antigen presentation. We compared the potency of differently loaded exosomes, directly loaded with OVA(323-339) peptide (Pep-Exo) or exosomes from OVA-pulsed DCs (OVA-Exo), for their ability to induce specific T-cell proliferation in vitro and in vivo. Both Pep-Exo and OVA-Exo elicited specific transgenic T-cell proliferation in vitro, with the Pep-Exo being more efficient. In contrast, only OVA-Exo induced specific T-cell responses in vivo highlighting the importance of indirect loading strategies in clinical applications. Coadministration of whole OVA overcame the unresponsiveness with Pep-Exo but still elicited a lower response compared with OVA-Exo. In parallel, we found that OVA-Exo not only augmented the specific T-cell response but also gave a Th1-type shift and an antibody response even in the absence of whole OVA. We detected IgG2a and interferon-gamma production from splenocytes showing the capability of exosomes to provide antigen for B-cell activation. Furthermore, we found that B cells are needed for exosomal T-cell stimulation because Bruton tyrosine kinase deficient mice showed abrogated B-and T-cell responses after OVA-Exo immunization. These findings reveal that exosomes are potent immune regulators and are relevant for the design of vaccine adjuvants and therapeutic intervention strategies to modulate immune responses. (Blood. 2009;113:2673-2683)