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犬骨髓来源树突状细胞的高效生成。

Efficient generation of canine bone marrow-derived dendritic cells.

作者信息

Isotani Mayu, Katsuma Kensuke, Tamura Kyoichi, Yamada Misato, Yagihara Hiroko, Azakami Daigo, Ono Kenichiro, Washizu Tsukimi, Bonkobara Makoto

机构信息

Department of Veterinary Clinical Pathology, Nippon Veterinary and Life Science University, Musashino-shi, Tokyo, Japan.

出版信息

J Vet Med Sci. 2006 Aug;68(8):809-14. doi: 10.1292/jvms.68.809.

Abstract

Because of their unsurpassed potency in presenting antigens to naive T cells, dendritic cells are considered to be an important candidate in the development of immunotherapeutic strategies. Despite the high potential of dendritic cell-based immunotherapy, as a so-called dendritic cell vaccination, few clinical approaches using dendritic cell vaccination have been performed in the dog because of very limited information regarding the generation of canine dendritic cells and their functional properties. We therefore established a protocol for the efficient generation of dendritic cells from canine bone marrow cells using recombinant feline granulocyte-macrophage colony-stimulating factor and canine interleukin-4. Dendritic cells were generated efficiently: a yield of 1-9 x 10(6) cells per approximately 0.5 ml of canine bone marrow aspiration was achieved. These dendritic cells showed features shared with mouse and human dendritic cells: dendrite morphology, expression of surface markers MHC class II and CD11c, and up-regulation of molecules related to antigen presentation (MHC class II, B7-1, and B7-2) by activation with lipopolysaccharide. Moreover, the dendritic cells demonstrated phagocytic activity, processing activity of pinocytosed proteins, and activation of allogeneic T cells far more potent than that by macrophages. Our findings suggest that the bone marrow-derived dendritic cells are functional for the capturing and processing of antigens and the initiation of T cell responses.

摘要

由于树突状细胞在向初始T细胞呈递抗原方面具有无与伦比的效力,因此被认为是免疫治疗策略开发中的重要候选者。尽管基于树突状细胞的免疫疗法具有很高的潜力,即所谓的树突状细胞疫苗接种,但由于关于犬树突状细胞的产生及其功能特性的信息非常有限,在犬中使用树突状细胞疫苗接种的临床方法很少。因此,我们建立了一种方案,使用重组猫粒细胞-巨噬细胞集落刺激因子和犬白细胞介素-4从犬骨髓细胞高效生成树突状细胞。树突状细胞被高效生成:每约0.5 ml犬骨髓抽吸物可产生1 - 9×10⁶个细胞。这些树突状细胞表现出与小鼠和人类树突状细胞共有的特征:树突形态、表面标志物MHC II类和CD11c的表达,以及通过脂多糖激活上调与抗原呈递相关的分子(MHC II类、B7 - 1和B7 - 2)。此外,树突状细胞表现出吞噬活性、胞饮蛋白的加工活性,以及激活同种异体T细胞的能力,远比巨噬细胞强。我们的研究结果表明,骨髓来源的树突状细胞在捕获和加工抗原以及启动T细胞反应方面具有功能。

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