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

Study of Tenascin-C on the thymocyte differentiation in mice

Tenascin-C对小鼠胸腺细胞分化的研究

基本信息

批准号：
11660304
负责人：
IKE Fumio
金额：
$ 2.05万
依托单位：
RIKEN (The institute of physical and chemical research)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11660304/
关键词：
thymus tenascin-C mouse early development T cell receptor beta chain repertoire formation CD25 CD44 プロT細胞

项目摘要

Tenascin-C (TN-C), one of the biggest extracellular matrix proteins, is expressed at considerable levels in the thymuses and spleens of adult mice. In order to investigate the function of TN-C in the immune system, we subjected TN-C deficient C3H/HeN congenic mice to sublethal X-irradiation. In the first week after irradiation, we found lineage negative-CD44 dull positive-CD25 positive thymocytes of TN-C deficient mice disappeared one day earlier than those of wild type mice. This strongly suggests that TN-C suppresses the differentiation of X-ray low sensitive thymic T cells which are believed as the major source of thymus reconstitution. We analyzed thymuses of wild-type mice biochemically and immunohistochemically. The expression of TN-C elevated strongly within a week after irradiation, and its expression was observed primarily at intra medullary lymphocytes and cortical blood vessels.On the functional assay using mixed lymphocyte reaction (MLR) method, responder cells from TN-C deficient GRS/A showed significantly low response to the stimulator cells from wild-type BALB/c than those from TN-C deficient BALB/c. This finding brought us the two possibilities ; one is that TN-C suppressed MLR overall via some suppressive factors or signals, and another is that TN-C worked to decrease the development of MLR reactive specific T cell clones. In order to clarify the latter possibility, we analyzed the T cell receptor β chain (Vβ) expression of peripheral lymph node T cells from TN-C deficient and wild-type GRS/A mice. However, we could not find any difference between them. On the contrary, FACS analyses of memory/activated T cells from non-stimulated spleens and lymph nodes indicated that the existence of TN-C might modify the induction of peripheral memory T cells.

腱生蛋白-C（Tenascin-C，TN-C）是最大的细胞外基质蛋白之一，在成年小鼠的胸腺和脾脏中以相当高的水平表达。为了研究TN-C在免疫系统中的作用，我们对TN-C缺陷的C_3H/HeN同源小鼠进行了亚致死量X射线照射。在照射后第一周，TN-C缺陷小鼠的T淋巴细胞系阴性-CD 44暗阳性-CD 25阳性的细胞比野生型小鼠早一天消失。这有力地表明，TN-C抑制X射线低敏感性胸腺T细胞的分化，这被认为是胸腺重建的主要来源。我们对野生型小鼠胸腺进行了生化和免疫化学分析。TN-C的表达在照射后一周内强烈升高，主要在髓内淋巴细胞和皮质血管中观察到。在混合淋巴细胞反应（MLR）方法的功能测定中，TN-C缺陷GRS/A的反应细胞对野生型BALB/c刺激细胞的反应显着低于TN-C缺陷BALB/c的反应细胞。这一发现给我们带来了两种可能性：一种是TN-C通过某些抑制因子或信号全面抑制MLR，另一种是TN-C减少了MLR反应性特异性T细胞克隆的形成。为了阐明后一种可能性，我们分析了TN-C缺陷型和野生型GRS/A小鼠外周淋巴结T细胞的T细胞受体β链（Vβ）表达。然而，我们找不到它们之间的任何区别。相反，来自非刺激的脾脏和淋巴结的记忆/活化T细胞的FACS分析表明TN-C的存在可能改变外周记忆T细胞的诱导。