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，最终导致移植排斥。 T细胞被认为是介导移植排斥的主要效应细胞。 T细胞的激活被认为需要至少两种不同的信号，即通过TCR传递的抗原特异性信号，以及使细胞能够继续产生IL-2并增殖的共刺激信号。在缺乏共刺激信号的情况下，T细胞仅做出部分反应并进入无反应状态。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同种异体移植排斥。在 BN 与 LEW 组合中，同种异体肺移植物在 7 天内被排斥。免疫组织化学研究显示，LFA-1阳性淋巴细胞在排斥过程中增加。双色流式细胞术分析显示，同种异体移植物中浸润性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，LFA-1 和 ICAM-1 抗体治疗不能完全防止移植排斥。然而，使用单克隆抗体的大鼠的移植物存活时间比未治疗的大鼠更长。我们现在正在研究单克隆抗体在肺移植中的作用。

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.