Aline Fleur, Bout Daniel, Amigorena Sébastian, Roingeard Philippe, Dimier-Poisson Isabelle
UFR des Sciences Pharmaceutiques, 31 Avenue Monge, 37200 Tours, France.
Infect Immun. 2004 Jul;72(7):4127-37. doi: 10.1128/IAI.72.7.4127-4137.2004.
It was previously demonstrated that immunizing mice with spleen dendritic cells (DCs) that had been pulsed ex vivo with Toxoplasma gondii antigens triggers a systemic Th1-biased specific immune response and induces protection against infection. T. gondii can cause severe sequelae in the fetuses of mothers who acquire the infection during pregnancy, as well as life-threatening neuropathy in immunocompromised patients, in particular those with AIDS. Here, we investigate the efficacy of a novel cell-free vaccine composed of DC exosomes, which are secreted antigen-presenting vesicles that express functional major histocompatibility complex class I and II and T-cell-costimulatory molecules. They have already been shown to induce potent antitumor immune responses. We investigated the potential of DC2.4 cell line-derived exosomes to induce protective immunity against toxoplasmosis. Our data show that most adoptively transferred T. gondii-pulsed DC-derived exosomes were transferred to the spleen, elicited a strong systemic Th1-modulated Toxoplasma-specific immune response in vivo, and conferred good protection against infection. These findings support the possibility that DC-derived exosomes can be used for T. gondii immunoprophylaxis and for immunoprophylaxis against many other pathogens.
先前已证明，用经体外弓形虫抗原脉冲处理的脾脏树突状细胞（DC）免疫小鼠会引发全身性Th1偏向的特异性免疫反应，并诱导对感染的保护作用。弓形虫可导致孕期感染的母亲的胎儿出现严重后遗症，以及免疫功能低下患者，特别是艾滋病患者出现危及生命的神经病变。在此，我们研究了一种由DC外泌体组成的新型无细胞疫苗的功效，DC外泌体是分泌的抗原呈递囊泡，表达功能性主要组织相容性复合体I类和II类以及T细胞共刺激分子。它们已被证明可诱导有效的抗肿瘤免疫反应。我们研究了DC2.4细胞系来源的外泌体诱导针对弓形虫病的保护性免疫的潜力。我们的数据表明，大多数过继转移的经弓形虫脉冲处理过的DC来源的外泌体被转移到脾脏，在体内引发强烈的全身性Th1调节的弓形虫特异性免疫反应，并提供良好的抗感染保护作用。这些发现支持DC来源的外泌体可用于弓形虫免疫预防以及针对许多其他病原体的免疫预防的可能性。
