Investigation on receptor systems mediating lymphocyte recirculation

介导淋巴细胞再循环的受体系统研究

• 批准号: 63570231
• 负责人: MIYASAKA Masayuki
• 金额: $ 1.34万
• 依托单位: Tokyo Metropolitan Institute of Medical Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1988
• 资助国家: 日本
• 起止时间: 1988 至 1989
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-63570231/
• 关键词: Lymphocyte; Lymphocyte recirculation; Homing; Endothelial cell; Cell adhesion; Adhesion molecule; Immunomodulation; 接着因子; ホーミング

In order to identify molecules involved in lymphocyte recirculation, particularly interactions between lymphocytes and HE (high endothelial) cells, we tried successfully to establish cultured cell lines derived from rat high endothelial venules (HEV). We then developed an in vitro assay with which to quantitate lymphocyte interaction with HE cells, a most important process in lymphocyte recirculation. We have made number of attempts to generate monoclonal antibodies (MAb) which can block this heterocellular interaction, and have subsequently obtained two MAb, one of which recognizes the rat ICAM-1, the other the rat LFA-1. By the use of the in vitro assay described above, we investigated the extent of contribution of the LFA-1 and ICAM-1 molecules in lymphocyte-HEV interaction. We have demonstrated that; (1) neither LFA-1 nor ICAM-1 plays a significant role in interaction between resting lymphocytes and HEV, (2) when lymphocytes are activated, LFA-1 dependent adhesion pathways becomes operative, although, depending on the extent of activation, ICAM- 1 dependent adhesion pathway is differentially used in the interaction between lymphocytes and HE cells. Further attempts are being made to identify molecules directly involved in lymphocyte-HE cell interaction.

为了鉴定参与淋巴细胞再循环的分子，特别是淋巴细胞与 HE（高内皮）细胞之间的相互作用，我们尝试成功建立源自大鼠高内皮微静脉（HEV）的培养细胞系。然后，我们开发了一种体外测定法，用于定量淋巴细胞与 HE 细胞的相互作用，这是淋巴细胞再循环中最重要的过程。我们进行了多次尝试来产生可以阻断这种异细胞相互作用的单克隆抗体(MAb)，并随后获得了两种MAb，其中一种识别大鼠ICAM-1，另一种识别大鼠LFA-1。通过使用上述体外测定，我们研究了LFA-1和ICAM-1分子在淋巴细胞-HEV相互作用中的贡献程度。我们已经证明； (1) LFA-1 和 ICAM-1 在静息淋巴细胞和 HEV 之间的相互作用中均不起重要作用，(2) 当淋巴细胞被激活时，LFA-1 依赖性粘附途径开始起作用，尽管根据激活程度，ICAM - 1 依赖性粘附途径在淋巴细胞和 HE 细胞之间的相互作用中被不同地使用。目前正在进一步尝试鉴定直接参与淋巴细胞-HE 细胞相互作用的分子。

项目成果

Tamatani,T.: "Identification of monoclonal antibodeies reactive with the rat homolog of ICAMー1,and evidence for a differential involvement of ICAMー1 in the adherence of resting vs.activated lymphocytes to high endothelial cells." International Immunology.

Tamatani, T.：“鉴定与 ICAM-1 大鼠同源物发生反应的单克隆抗体，以及 ICAM-1 在静息淋巴细胞与活化淋巴细胞对高内皮细胞粘附中的不同参与的证据。”

宮坂昌之、桂義元: "Annual Review免疫1989" 中外医学社, 1-9 (1989)

Masayuki Miyasaka、Yoshimoto Katsura：“免疫学年度评论 1989”Chugai Igakusha，1-9 (1989)

Toyama, N: "Interaction between lymphocytes and endothelial cells - Its molecular basis (Japanese)" Byori-To-Rinsho 8:279-284, 1990.

Toyama, N：“淋巴细胞和内皮细胞之间的相互作用 - 其分子基础（日语）”Byori-To-Rinsho 8：279-284，1990。

宮坂昌之: "T細胞分化と膜抗原" 臨床免疫. 21. 1006-1021 (1989)

Masayuki Miyasaka：“T 细胞分化和膜抗原”临床免疫学 21. 1006-1021 (1989)。

宮坂昌之、玉谷卓也: 臨床免疫. 21. 173-184 (1989)

Masayuki Miyasaka，Takuy​​a Tamaya：临床免疫学。21. 173-184 (1989)