A potential immunosuppressive effect of anti-lymphocyte function-associated antigen-1 monoclonal antibody on islet transplantation.
A potential immunosuppressive effect of anti-lymphocyte function-associated antigen-1 monoclonal antibody on islet transplantation.
复制标题
抗淋巴细胞功能相关抗原 1 单克隆抗体对胰岛移植的潜在免疫抑制作用。
作者：
M. Gotoh;T. Fukuzaki;M. Monden;K. Dono;T. Kanai;H. Yagita;K. Okumura;T. Mori
在小鼠胰岛移植中检测了针对淋巴细胞功能相关抗原-1（LFA-1）和CD 2分子的mAb的免疫抑制潜力。将来自BALB/c（H-2d）小鼠的粗消化的胰岛移植到链脲佐菌素诱导的糖尿病C57 BL/6（H-2b）小鼠的肾包膜下空间。移植后立即和移植后第一天以0.1 mg/小鼠/天的剂量腹腔内注射KBA（抗LFA-1）和RM 2 -1（抗CD 2）的大鼠mAb。在未治疗的动物中，胰岛同种异体移植物发生急性排斥反应，平均存活时间（MST）为19.6 +/- 8.3天。对照同种型匹配的抗CD 18治疗未延长12.8 +/- 1.6天的MST。单独抗LFA-1治疗在10名接受者中的5名中产生了无限期存活，MST为72.2 +/- 33.4天。抗CD 2治疗未能做到这一点，尽管MST略微延长至32.8 +/- 20.5天。当两种mAb一起给药时，未观察到抗CD 2治疗的额外获益（MST：77.4 +/- 31.1天）。尽管对胰岛同种异体移植物无反应，但动物没有遭受任何严重的感染性疾病。携带长期功能性胰岛的小鼠排斥第三方皮肤移植物以及胰岛供体品系皮肤移植物。长期存活的同种异体胰岛移植物也发生了排斥反应。这些结果表明，围手术期短疗程的抗LFA-1单克隆抗体治疗可以诱导对胰岛同种异体移植物的无反应性，尽管它不是全身性的，并且通过这些粘附分子的共刺激信号在诱导导致同种异体移植胰岛排斥的免疫应答中起核心作用。
The immunosuppressive potentials of mAbs to lymphocyte function-associated antigen-1 (LFA-1) and CD2 molecules were examined in murine islet transplantation. Crude digested islets from BALB/c (H-2d) mice were transplanted into the renal subcapsular space of streptozotocin-induced diabetic C57BL/6 (H-2b) mice. The rat mAbs of KBA (anti-LFA-1) and RM2-1 (anti-CD2) were given intraperitoneally immediately after transplantation and on the first day after grafting at a dose of 0.1 mg/mouse/day. In nontreated animals, the islet allografts were acutely rejected with a mean survival time (MST) of 19.6 +/- 8.3 days. Control isotype-matched anti-CD18 treatment did not prolong the MST of 12.8 +/- 1.6 days. Anti-LFA-1 treatment alone produced indefinite survival in 5 of 10 recipients with MST of 72.2 +/- 33.4 days. Anti-CD2 treatment failed to do so, although MST was marginally prolonged to 32.8 +/- 20.5 days. When both mAbs were given together, additional benefit with anti-CD2 treatment was not observed (MST: 77.4 +/- 31.1 days). In spite of the unresponsiveness to islet allografts, the animals did not suffer from any severe infectious disease. Mice bearing long-term functioning islets rejected third-party skin grafts as well as islet donor strain skin grafts. The long-term surviving islet allografts were also rejected coincidentally. These results indicate that a perioperative short course of anti-LFA-1 mAb treatment can induce unresponsiveness to islet allografts, although it is not systemic, and that costimulatory signals through these adhesion molecules play a central role in inducing an immune response leading to rejection of the allografted islets.