Ohta Y, Gotoh M, Ohzato H, Fukuzaki T, Nishihara M, Dono K, Umeshita K, Sakon M, Yagita H, Okumura K, Tanaka T, Kawashima H, Miyasaka M, Monden M
Department of Surgery II, Osaka University Medical School, Japan.
Transplantation. 1998 Apr 27;65(8):1094-100. doi: 10.1097/00007890-199804270-00014.
Cellular interactions that lead to graft rejection were examined in a rat-to-mouse xenogeneic combination using species-specific monoclonal antibodies (mAbs) against donor and recipient intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) molecules, respectively. Although both mAbs displayed moderate blocking activity in an in vitro mixed lymphocyte response assay, strong suppression was observed when anti-donor (rat) ICAM-1 mAb was combined with anti-recipient (mouse) LFA-1 mAb. Likewise, significant prolongation of islet xenograft survival was observed with these mAbs. Thus, 0.05 mg of anti-mouse LFA-1 mAb and anti-rat ICAM-1 mAb given on days 0 and 1 produced significant prolongation of graft survival over the control (51+/-20 days vs. 10+/-3 days, P<0.0001), but not when anti-mouse ICAM-1 mAb was combined with anti-mouse LFA-1 mAb (13+/-3 days). In this species combination, mouse T cells were able to proliferate in the presence of rat antigen-presenting cells (APCs) in a cell number-dependent manner, but not in the presence of mouse APCs. The binding assay showed that LFA-1 molecules on mouse T cells can bind immobilized rat ICAM-1 molecules. These results suggest that rat ICAM-1 molecules on APCs can interact with mouse LFA-1 molecules on T cells across a species barrier and that this binding generates the consequent immune responses leading to rejection. mAb treatment against these adhesion molecules of recipient as well as donor is crucial for preventing rejection in a xenogeneic transplantation model.
使用分别针对供体和受体细胞间黏附分子-1（ICAM-1）及淋巴细胞功能相关抗原-1（LFA-1）分子的种属特异性单克隆抗体（mAb），在大鼠到小鼠的异种组合中研究了导致移植物排斥的细胞间相互作用。尽管两种mAb在体外混合淋巴细胞反应试验中均表现出适度的阻断活性，但当抗供体（大鼠）ICAM-1 mAb与抗受体（小鼠）LFA-1 mAb联合使用时，观察到了强烈的抑制作用。同样，使用这些mAb可观察到胰岛异种移植物存活时间显著延长。因此，在第0天和第1天给予0.05 mg抗小鼠LFA-1 mAb和抗大鼠ICAM-1 mAb，与对照组相比，移植物存活时间显著延长（51±20天对10±3天，P<0.0001），但抗小鼠ICAM-1 mAb与抗小鼠LFA-1 mAb联合使用时则不然（13±3天）。在这种种属组合中，小鼠T细胞能够在大鼠抗原呈递细胞（APC）存在的情况下以细胞数量依赖的方式增殖，但在小鼠APC存在的情况下则不能。结合试验表明，小鼠T细胞上的LFA-1分子可以结合固定化的大鼠ICAM-1分子。这些结果表明，APC上的大鼠ICAM-1分子可以跨越种属屏障与T细胞上的小鼠LFA-1分子相互作用，并且这种结合会引发导致排斥的后续免疫反应。针对受体以及供体的这些黏附分子进行mAb治疗对于在异种移植模型中预防排斥至关重要。
