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Establishment of antigen specific regulatory dendritic cells and treatment of VKH disease with these dendritic cells

抗原特异性调节树突细胞的建立以及用这些树突细胞治疗VKH病

基本信息

批准号：
16591739
负责人：
YAMAKI Kunihiko
金额：
$ 2.24万
依托单位：
Nippon Medical School (2005)Akita University (2004)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

We have analyzed whether in vitro prepulsed dendritic cells have the capability to induce the autoimmune disease. The dendritic cells of C57BL/6 mice were collected with anti-CD11c magnetic beads system and cultured in RPMI1640 containing GM-CSF. These cells were pulsed with TRP-1 peptides. These TRP-1 peptides prepulesd dendritic cells were further cultured with CD40 and LPS. Thus prepulsed and matured dendritic cells were injected into naive C57BL/6 mice.The mice injected with these dendritic cells had developed autoimmune disease. The clinical findings of this disease were featured with depigmentation and poliosis of skin. However inflammatory changes of the intraocular tissues were not clearly seen by ordinally observation.Histologically, many inflammatory cells were seen around the hair follicles and some glands. Skin ulcers were seen in the lesions where the inflammatory cells infiltrate into the dermis and under the dermis. In the depigmented and/or poliosis regions, granulomas were formed with larges cells that contain many pigments.In the intra ocular tissues, granulomas were formed in the iris and choroid. All these findings were very similar to the findings of VKH disease.Next, we cultured the prepulsed dendritic cells with IL-10 and TGF-β to keep immature stage. These immature cells were injected to naive mice and the inhibitory effects of the cells were tested. In contrast to our speculation, no inhibitory effects were detected by injection of these immature dendritic cells. We are now studying the mechanism of these results.

我们分析了体外预脉冲树突状细胞是否具有诱导自身免疫性疾病的能力。采用抗cd11c磁珠系统采集C57BL/6小鼠树突状细胞，在含有GM-CSF的RPMI1640中培养。这些细胞被TRP-1肽脉冲。将这些TRP-1肽进一步用CD40和LPS培养树突状细胞。因此，将预脉冲和成熟的树突状细胞注射到幼稚的C57BL/6小鼠体内。注射这些树突状细胞的小鼠患上了自身免疫性疾病。该疾病的临床表现为皮肤色素沉着和脊髓灰质炎。常规观察眼内组织炎性改变不明显。组织学上，毛囊和部分腺体周围可见许多炎性细胞。皮损处可见皮肤溃疡，炎症细胞浸润到真皮层和真皮层下。在脱色区和/或脊髓灰质炎区，肉芽肿由含有许多色素的大细胞形成。眼内组织中，虹膜和脉络膜形成肉芽肿。所有这些结果与VKH病的结果非常相似。下一步，我们用IL-10和TGF-β培养预脉冲树突状细胞以保持未成熟阶段。将这些未成熟细胞注射到未成熟小鼠体内，并检测细胞的抑制作用。与我们的推测相反，注射这些未成熟的树突状细胞没有检测到抑制作用。我们正在研究这些结果的机理。