Sudies on the differention and activation mechanisms of T cell via lymphocye functioning antigen (LFA).

本研究旨在了解T细胞上的淋巴细胞功能相关抗原（莱亚）如何参与各种免疫应答。为了分析其作用机制，我们首先利用小鼠心脏移植实验系统，研究了体内给药对诱导免疫耐受的影响。然后，揭示了来自LFA-1的共刺激信号的缺失可诱导T细胞无反应性。为了研究T细胞耐受的更详细的机制，我们进一步分析了其他LFA在T细胞无反应性诱导方面的作用。然后，我们进一步分析了其他莱亚对T细胞的作用以及这些配体分子对抗原提呈抗原（APC）的作用。在研究过程中，我们确定了CD 48为小鼠CD 2的未知配体。利用这些分子的单克隆抗体，我们可以检测CD 2和CD 48/LFA-3通路的生物学意义。关于T细胞表面的CD 28信号，我们成功地鉴定出APC上的未知配体，并命名为B70（CD 86）。利用B70的cDNA和单克隆抗体，我们可以进一步研究CD 28和CD 80/CD 86通路在T细胞免疫应答的启动以及T细胞免疫耐受的无能诱导和/或维持中的重要作用。特别是在体内实验系统中，抗CD 80和抗CD 86的应用可以诱导接受同种异体移植的供体产生永久耐受。

We performed the study to know how lymphocyte function associated antigens (LEA) on T cell are involved in various kind of immune responses. To analyzes it's mechanisms, we at first reported the effect of in vivo administration on the induction of tolerance by using mouse heart allograft experimental system. Then, it was revealed that absence of costimulatory signals from LFA-1 could induce T cell anergy. To investigate more detailed mechanisms of T cell tolerance, we further analyzed the role of other LFA in terms of T cell anergy induction. Then, we further analyzed the role of other LEA on T cell as well as those ligand molecules on antigen presenting all (APC). On the way of study, we could identify CD48 as unknown ligand of mouse CD2. By using monoclonal antibody to those molecules which we established, we could examine the biological significance of CD2 and CD48/LFA-3 pathway. Regarding to the signals from CD28 of T cell, we succeeded to identify unknown ligand on APC and name B70 (CD86). By using cDNA of B70 as well as monoclonal antibody, we could expand the study how CD28 and CD80/CD86 pathway is important to understand the intiation of T cell immune reponse as well as anergy induction and/or maintenance of T cell torelance. Especially using in vivo experimental systems, the administration of antiCD80 and antiCD86 could induce permanent torelance in the donor received allograft.