Red blood cells as innovative antigen carrier to induce specific immune tolerance
Red blood cells as innovative antigen carrier to induce specific immune tolerance
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DOI：
10.1016/j.ijpharm.2012.12.044
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发表时间：
2013-02-25
影响因子：
5.8
通讯作者：
Godfrin, Yann
中科院分区：
文献类型：
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作者：
Cremel, Magali;Guerin, Nathalie;Godfrin, Yann
抗原的给药途径、剂量以及靶向的抗原呈递细胞（APC）类型是诱导免疫耐受的重要因素。尽管在动物模型中获得了令人鼓舞的结果，但由于抗原递送效率低，静脉内注射可溶性抗原在自身免疫性疾病的人类临床试验中是不成功的。为了改善抗原递送，我们使用小鼠红细胞（RBC）作为抗原载体来特异性靶向APC，所述APC负责在吞噬后去除衰老的RBC。在这项研究中，我们证明了红细胞的抗原递送诱导的体液反应强烈下降相比，卵清蛋白（OVA）游离形式的小鼠。此外，用[双（磺基琥珀酰亚胺基）]辛二酸酯（BS 3）（一种已知可增强RBC吞噬作用的化合物）处理的OVA-负载RBC诱导抗原特异性T细胞应答的抑制和调节性T细胞百分比的增加。诱导的耐受状态是持久的、抗原特异性的并且足够稳健以耐受用与霍乱毒素佐剂混合的抗原的免疫。与已经使用的全身性免疫抑制剂治疗相比，这种RBC策略不会消除免疫系统，构成了诱导耐受性的有吸引力的方法。(C)2013爱思唯尔有限公司版权所有。
The route of administration, the dose of antigen as well as the type of antigen-presenting cells (APCs) targeted are important factors to induce immune tolerance. Despite encouraging results obtained in animal models, intravenous injection of soluble antigen is unsuccessful in human clinical trials on autoimmune disease due to inefficient antigen delivery. To improve antigen delivery, we used mouse red blood cells (RBCs) as antigen vehicles to specifically target APCs which are responsible for removal of senescent RBCs after phagocytosis. In this study, we demonstrated that antigen-delivery by RBCs induced a strong decrease in the humoral response compared with the ovalbumin (OVA) free form in mice. In addition, OVA-loaded RBC treated with [bis(sulphosuccinimidyl)] suberate (BS3), a chemical compound known to enhance RBC phagocytosis, induced an inhibition of antigen-specific T cell responses and an increase in the percentage of regulatory T cells. The state of tolerance induced is long lasting, antigen-specific and sufficiently robust to withstand immunization with antigen mixed with cholera toxin adjuvant. This RBC strategy, which does not abolish the immune system, constitutes an attractive approach for induction of tolerance compared to systemic immunosuppressant therapies already in use. (C) 2013 Elsevier B.V. All rights reserved.