Significance of adhesion molecules in differentiation and activation of thymocytes.

粘附分子在胸腺细胞分化和激活中的意义。

• 批准号: 01480167
• 负责人: MATSUURA Akihiro
• 金额: $ 4.29万
• 依托单位: Sapporo Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1989
• 资助国家: 日本
• 起止时间: 1989 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-01480167/
• 关键词: thymocytes; adhesion molecules; extracelluar matrix; cDNAクロ-ニング; T細胞活性化; 単クロ-ン抗体

In the sequential steps in the T lymphocyte differentiation, the traffic of T cell progenitors through thymic tissue and contact with the thymic stromal cells have been considered to be most crucial, and stromal cells have been regarded as the most effective partner of this contact. Extracellular matrix, such as fibronectin (FN), are ubiquitously distributed within the body and considered to be involved in the first step of cell adhesion. For the lymphoid cells which do not have strong contacts with adjacent cells, the adhesion to thymic stromal cells or extracellular matrix must be very important for the initial differentiational process occurred in thymic microenvironments. To elucidate the function of adhesion molecules on T cell development and activation, we have generated monoclonal antibodies, 7D3 and 8H3, which respectively inhibit thymocyte adhesion either to thymic epithelial cells or fibronectin. Furthermore, 8H3 antibody stimulate thymocyte proliferation. Since both antigens were already expressed on immature thymocytes which do not yet express T cell receptor complex, such antigen-independent interactions may play crucial roles in early T cell development. Based on partial amino acids sequences of affinity-purified 8H3 polypeptides, putative cDNA clones encoding 8H3 molecules were isolated and further study to identify primary structure of the cDNA clones are in progress.

在T淋巴细胞分化的连续步骤中，T细胞祖细胞通过胸腺组织的运输以及与胸腺基质细胞的接触被认为是最关键的，而基质细胞被认为是这种接触的最有效伙伴。细胞外基质，如纤连蛋白 (FN)，在体内广泛分布，被认为参与细胞粘附的第一步。对于与邻近细胞没有很强接触的淋巴细胞来说，与胸腺基质细胞或细胞外基质的粘附对于胸腺微环境中发生的初始分化过程一定非常重要。为了阐明粘附分子对 T 细胞发育和激活的功能，我们制备了单克隆抗体 7D3 和 8H3，它们分别抑制胸腺细胞与胸腺上皮细胞或纤连蛋白的粘附。此外，8H3 抗体刺激胸腺细胞增殖。由于两种抗原均已在尚未表达 T 细胞受体复合物的未成熟胸腺细胞上表达，因此这种不依赖于抗原的相互作用可能在早期 T 细胞发育中发挥至关重要的作用。基于亲和纯化的8H3多肽的部分氨基酸序列，分离了编码8H3分子的推定cDNA克隆，并且正在进行进一步研究以确定cDNA克隆的一级结构。

项目成果

菊地 浩吉,上出 利光: "新リンパ球機能検索法 改訂4版 矢田 純一,藤原 道夫編著(組識におけるリンパ球亜群の同定,腫瘍免疫に用いられる主な手段(ヒトを中心に),killer細胞活性の測定法)" 中外医学社,東京, 34 (1990)

Kokichi Kikuchi，Toshimitsu Kamide：“新淋巴细胞功能搜索方法，修订版第4版，Junichi Yada，Michio Fujiwara（编）（组织中淋巴细胞亚群的识别，用于肿瘤免疫的主要方法（主要在人类），杀手）“方法用于测量细胞活性）”Chugai Igakusha，东京，34（1990）

Nomura, N., Uno, E., Tamura, Y., Suzuki, A., Kikuchi, K. and Uede, T.: "Vascular endothelial cells capable of binding lymphocytes express R2-1A6 antigen." Life Science Advances.

Nomura, N.、Uno, E.、Tamura, Y.、Suzuki, A.、Kikuchi, K. 和 Uede, T.：“能够结合表达 R2-1A6 抗原的淋巴细胞的血管内皮细胞。”

Torimoto, Y., Kinebuchi, M., Matsuura, A., Kikuchi, K., and Uede, T.: "A monoclonal antibody 8H3 which reacts with rat T cell and augment in vitro T cell proliferative responses." J. Exp. Med.172. 1315-1323 (1990)

Torimoto, Y.、Kinebuchi, M.、Matsuura, A.、Kikuchi, K. 和 Uede, T.：“一种单克隆抗体 8H3，可与大鼠 T 细胞反应并增强体外 T 细胞增殖反应。”

Uehira,M.,Uno,M.,Kurner,T.,Kikutani,H.,Mori,K.,Inomoto,T.,Uede,T.,Miyazaki,J.,Nishimoto,H.,Kishimoto,T.and Yamamura,K.: "Development of autoimmune insulitis is prevented in E^d but not A^k NOD transgenic mice." International Immunology. 1. 209-213 (1989)

上平，M.，宇野，M.，库纳，T.，菊谷，H.，森，K.，猪本，T.，上德，T.，宫崎，J.，西本，H.，岸本，T.和

Lupin,D.,Iwaki,H.,Masuda,A.,Imamura,M.and Uede,T.: "The preferential binding of immature thymocytes to a rat thymic epithelial cell line." Thymus. 14. 243-259 (1989)

Lupin,D.、Iwaki,H.、Masuda,A.、Imamura,M. 和 Uede,T.：“未成熟胸腺细胞与大鼠胸腺上皮细胞系的优先结合。”