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

器官移植后遇到的关键问题是同种异体免疫反应，最终导致移植物排斥反应。T细胞被认为是介导移植排斥反应的主要效应细胞。T细胞的激活被认为至少需要两个不同的信号，通过TCR传递的抗原特异性信号，以及使细胞能够继续产生和增殖IL-2的共刺激信号。在没有共刺激信号的情况下，T细胞只做出部分反应，进入无反应状态。在本研究中，我们研究了抗LFA-1和ICAM-1抗体治疗是否能预防大鼠肺移植排斥反应。BN-LEW联合组移植肺在7d内发生排斥反应。免疫组织化学研究发现，LFA-1阳性淋巴细胞在排斥反应过程中逐渐增多。双色流式细胞仪分析显示，移植物中浸润性T细胞表面LFA-1和ICAM-1分子的表达强度增强。在心脏移植物中，LFA-1和ICAM-1抗体的治疗不能完全阻止移植物排斥反应的发生。然而，应用单抗的大鼠移植物存活时间长于未经治疗的大鼠。我们现在正在研究单抗在肺移植中的作用。

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.