权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Differential localization of CD4ィイD1+ィエD1 T lymphocyte subsets.

CD4D1+D1 T 淋巴细胞亚群的差异定位。

基本信息

批准号：
10670121
负责人：
SHIMIZU Akira
金额：
$ 2.05万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

A vast majority of CD4+ T cells infiltrating into gastric mucosa and in the gastric lymph node shows activated memory phenotype, CD45RBィイD1lowィエD1 L-selectinィイD1lowィエD1 CD44ィイD1highィエD1, in neonataly thymectomized BALB/c mice bearing autoimmune gastritis (AIG), indicating that these cells are actively involved in this disease. CD4ィイD1+ィエD1 T cells of gastric lymph node expressed both of mRNAs encoding IFN-γ and IL-4. However, those infiltrating into gastric mucosa expressed very low level of IL-4 mRNA, even though they strongly expressed IFN-γ mRNA. Among CD4ィイD1+ィエD1 T cells separated from AIG mice expressing detectable levels of either IFN-γ or IL-4 by intracellular staining, only less than one seventh expressed IL-4 and thus most of them expressed IFN-γ in gastric mucosa whereas roughly the half and one third expressed IL-4 in gastric lymph node and spleen, respectively. These findings indicate that the Th1 cells predominantly infiltrate into autoimmune lesions and Th2 cells are mainly resident in the regional lymph node. We further set up an in vitro model system of transendothelial migration using a murine endothelial cell line. F-2. and found that Th1 cells in CD4ィイD1+ィエD1 T cells separated from lymphoid tissues of AIG mice preferentially passed through the monolayer of endothelial cells while little portion of Th2 cells did so. Such different ability of transendothelial migration and localization might explain the dominance of Th1 cells destroying the tissue in focal lesion without inhibition by the Th2 cells, in spite of both of subsets simultaneously activated in AIG mice and the functions of each T cell subset seem to be mutually exclusive. Using Th1 and Th2 cells, taken from normal or TCR transgenic mice and induced in vitro, such differential transendothelial migration was reproduced. Therefore preferential transendothelial migration seems to be a general character of Th1 cells.

在去胸腺的自身免疫性胃炎小鼠中，绝大多数CD_4~+T细胞在胃粘膜和胃淋巴结内表现为激活的记忆表型：CD45RbィイD_1lowィエD_1低ィエ_1 L-选择素D_1低ィエD_1 CD_44ィイD_1高ィエD_1，表明这些细胞积极参与了自身免疫性胃炎。胃淋巴结CD 4ィイD 1+ィエD 1 T细胞同时表达干扰素γ和IL 4。而浸润性胃黏膜组织中IL-4mRNA表达水平很低，但表达较强的干扰素-γ。从免疫球蛋白小鼠分离的CD4Th1+ィイ+ィエD1T细胞中，只有不到七分之一的T细胞表达IL-4，其中大部分在胃粘膜表达干扰素-γ，而大约一半和三分之一的T细胞分别在胃淋巴结和脾中表达IL-4。提示Th1细胞主要渗入自身免疫性病变，Th2细胞主要位于区域淋巴结。我们进一步利用小鼠内皮细胞系建立了跨内皮细胞迁移的体外模型系统。F-2。从免疫球蛋白小鼠淋巴组织分离的CD4Th1+ィイD1T细胞中，Th1细胞优先通过内皮细胞单层，而Th2细胞仅有少量通过内皮细胞单层。这种不同的跨内皮细胞迁移和定位能力可能解释了为什么Th1细胞在局灶性病变中破坏组织而不被Th2细胞抑制，尽管在AIG小鼠中这两个亚群同时被激活，而且每个T细胞亚群的功能似乎是相互排斥的。使用取自正常或TCR转基因小鼠的Th1和Th2细胞，并在体外诱导，复制了这种差异的跨内皮细胞迁移。因此，优先经内皮细胞迁移似乎是Th1细胞的一个共性。