Prevention of pulmonary allograft rejection by treatment with antibodies to LFA-1 and ICAM-1.

通过 LFA-1 和 ICAM-1 抗体治疗预防肺同种异体移植排斥。

• 批准号: 04670821
• 负责人: HIRONO Tatshuhiko
• 金额: $ 1.34万
• 依托单位: Niigata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04670821/
• 关键词: Pulmonary transplantation; LFA-1; ICAM-1; Monoclonal antibody; Rat; 拒絶反応; ラット; モノクローナル抗体治療; 心臓移植; 抗体治療

The key problem encountered following organ transplantation is the allogeneic immune response, which ultimately leads to graft rejection. T cells are thought to be the main effector cells which mediate graft rejection. The activation of T cells is thought to require at least two distinct signals, antigen specific signal delivered via the TCR, as well as a co-stimulatory signal which enables the cell to proceed to IL-2 producion and proliferation. In the absence of the co-stimulatory signal, the T cell makes only a partial response and enters unresponsive state. In the present study, we investigated whether the treatment with antibodies to LFA-1 and ICAM-1 could prevent pulmonary allograft rejection in rats. In BN to LEW combination, pulmonary allograft was rejected within 7 days. In the immunohistochemical study, LFA-1-positive lymphocytes increased in the course of rejection. Two color flow cytometry analysis revealed that the intensity of LFA-1 and ICAM-1 molecules on the infiltrating T cells in the allograft increased. In the cardiac allograft, treatment with antibodies to LFA-1 and ICAM-1 could not prevent graft rejection completely. However graft survival of rats with mAbs was longer than that of rats without treatment. We are now investigating the ettects of mAbs in pulmonary transplantation.

器官移植后遇到的关键问题是同种异体免疫反应，其最终导致移植物排斥。T细胞被认为是介导移植物排斥反应的主要效应细胞。T细胞的活化被认为需要至少两种不同的信号，通过TCR递送的抗原特异性信号，以及使细胞能够进行IL-2产生和增殖的共刺激信号。在缺乏共刺激信号的情况下，T细胞仅产生部分应答并进入无应答状态。在本研究中，我们研究了LFA-1和ICAM-1抗体治疗是否可以预防大鼠肺移植排斥反应。在BN与LEW的组合中，肺同种异体移植物在7天内发生排斥反应。在免疫组化研究中，LFA-1阳性淋巴细胞在排斥反应过程中增加。双色流式细胞仪分析显示，移植物中浸润T细胞上的LFA-1和ICAM-1分子的强度增加。在同种异体心脏移植中，抗LFA-1和ICAM-1抗体治疗不能完全预防移植物排斥反应。然而，与单克隆抗体的大鼠移植物的存活时间比未处理的大鼠。我们正在研究单克隆抗体在肺移植中的作用。