Shiraishi Takeshi, Yasunami Yohichi, Takehara Megumi, Uede Toshimitsu, Kawahara Katsunobu, Shirakusa Takayuki
Department of Surgery II, Fukuoka University School of Medicine, Japan.
Am J Transplant. 2002 Mar;2(3):223-8. doi: 10.1034/j.1600-6143.2002.20306.x.
CTLA4 immunoglobulin (CTLA4Ig), which binds with a high affinity to B7-1 and B7-2, interrupts T-cell activation by inhibiting costimulatory signal. CTLA4Ig has been used in hopes of achieving antigen-specific tolerance induction in several solid organ transplants. In lung allograft rejection, however, its use has been controversial in terms of its effect on prevention of rejection. In the present study, the effect of murine CTLA4Ig on rat-lung allograft rejection was investigated. Rat left-lung transplantation was performed in an RT1 incompatible donor (Brown Norway; BN)-recipient (F344) combination. All allografts (n = 12) without any treatment were rejected within 7 days after transplantation. A single injection of murine form CTLA41g at a dose of 100 microg intraperitoneally (ip) or intravenously (iv) on day 1 post-transplantation achieved long-term graft survival (>90days) in 2/5 (40%) and 3/8 (38%), respectively. Moreover, 6/7 (86%) allografts in rats that received iv injection of 500 microg CTLA4Ig survived more than 90days. Allograft survival in the CTLA4Ig 500 microg iv recipient group was significantly longer than that in the no-treatment control or control immunoglobulin group (p <0.01). Four out of seven recipients bearing functional allografts for more than 90 days with the CTLA4Ig treatment accepted donor-specific skin grafts, whereas all third-party skin grafts (n=3) were rejected. Prevention of rat-lung allograft rejection could be achieved by intravenous administration of CTLA4Ig, resulting in long-term allograft survival with acceptance of donor-specific skin grafts.
细胞毒性T淋巴细胞相关抗原4免疫球蛋白（CTLA4Ig）能与B7-1和B7-2高亲和力结合，通过抑制共刺激信号来阻断T细胞活化。人们一直希望通过使用CTLA4Ig在多种实体器官移植中实现抗原特异性的免疫耐受诱导。然而，在肺移植排斥反应中，其在预防排斥反应方面的效果一直存在争议。在本研究中，我们探究了鼠源CTLA4Ig对大鼠肺移植排斥反应的影响。在RT1不相容的供体（棕色挪威大鼠；BN）-受体（F344）组合中进行大鼠左肺移植。所有未经任何处理的同种异体移植物（n = 12）在移植后7天内均被排斥。移植后第1天腹腔内（ip）或静脉内（iv）单次注射剂量为100微克的鼠源形式CTLA4Ig，分别使2/5（40%）和3/8（38%）的移植物获得了长期存活（>90天）。此外，静脉注射500微克CTLA4Ig的大鼠中，6/7（86%）的同种异体移植物存活超过90天。CTLA4Ig 500微克静脉注射受体组的同种异体移植物存活时间显著长于未处理对照组或对照免疫球蛋白组（p <0.01）。接受CTLA4Ig治疗且功能正常的同种异体移植物存活超过90天的7只受体中，有4只接受了供体特异性皮肤移植，而所有第三方皮肤移植（n = 3）均被排斥。静脉注射CTLA4Ig可预防大鼠肺移植排斥反应，从而使同种异体移植物长期存活，并接受供体特异性皮肤移植。
