Cavazzana-Calvo M, Sarnacki S, Haddad E, De Coene C, Calise D, Yvon E, Cerf-Bensussan N, Fischer A
INSERM U132, Hôpital Necker-Enfants Malades, Paris, France.
Transplantation. 1995 Jun 15;59(11):1576-82.
The aim of the present study was to compare the preventive effect of a nondepleting monoclonal antibody specific for the LFA-1 alpha chain (CD11a) on the rejection of bone marrow, vascularized cardiac, and nonvascularized skin grafts in the same haplotype-disparate mouse strain combination. A 7-day treatment with a total dose of 0.5 mg of anti-LFA-1 antibody (H-129) had no effect on the rejection of BDF1(H-2b/d) skin grafts by CDF1 (H-2k/d)-treated mice. In contrast, the same treatment regimen significantly prolonged the survival of BDF1 cardiac allografts in CDF1 mice: 7 out of 10 mice had a functional graft after 70 days, whereas all control mice had rejected their graft by 11 days. Nevertheless, cardiac allografts were ultimately rejected. In contrast, infusion of anti-LFA-1 antibody was able to promote definitive engraftment of T-depleted BDF1 marrow in 9 gray-irradiated CDF1 recipients: in surviving mice, engraftment increased from 10% in controls to 78% in antibody-treated recipients. In mice that tolerated their cardiac graft for more than 70 days, there was a slight delay in the rejection of donor skin graft but no in vitro evidence of tolerance. In contrast, mice with successful marrow engraftment did not reject donor skin graft and failed to mount proliferative and cytotoxic responses against donor alloantigens, whatever the percentage of engrafted donor leukocytes. These results indicate that a nondepleting anti-LFA-1 antibody can efficiently protect against rejection of MHC-incompatible heart and bone marrow. The protective effect of anti-LFA-1 antibody was associated with the induction of T cell tolerance toward donor antigens after bone marrow transplantation.
本研究的目的是比较一种针对淋巴细胞功能相关抗原-1α链（CD11a）的非耗竭性单克隆抗体，在相同单倍型不同的小鼠品系组合中，对骨髓、血管化心脏和非血管化皮肤移植排斥反应的预防效果。用总剂量为0.5mg的抗LFA-1抗体（H-129）进行为期7天的治疗，对经CDF1（H-2k/d）处理的小鼠排斥BDF1（H-2b/d）皮肤移植没有影响。相比之下，相同的治疗方案显著延长了CDF1小鼠体内BDF1心脏同种异体移植物的存活时间：10只小鼠中有7只在70天后仍有功能正常的移植物，而所有对照小鼠的移植物在11天前就已被排斥。然而，心脏同种异体移植物最终还是被排斥了。相比之下，输注抗LFA-1抗体能够促进9只经灰色照射的CDF1受体小鼠中T细胞耗竭的BDF1骨髓的最终植入：在存活的小鼠中，植入率从对照组的10%增加到抗体处理组受体的78%。在耐受心脏移植超过70天的小鼠中，供体皮肤移植排斥反应略有延迟，但没有体外耐受的证据。相比之下，骨髓植入成功的小鼠不排斥供体皮肤移植，并且无论植入的供体白细胞百分比如何，都无法对供体同种异体抗原产生增殖和细胞毒性反应。这些结果表明，一种非耗竭性抗LFA-1抗体能够有效预防MHC不相容的心脏和骨髓的排斥反应。抗LFA-1抗体的保护作用与骨髓移植后T细胞对供体抗原的耐受性诱导有关。
