Sankary H N, Yin D P, Chong A S, Ma L L, Blinder L, Shen J K, Foster P, Williams J W
Department of General Surgery, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, USA.
Transplantation. 1998 Oct 15;66(7):832-7. doi: 10.1097/00007890-199810150-00004.
In the experiment described here, we investigated the effects of the immunosuppressants FK506 and leflunomide (Lef) on the survival of hamster hearts and liver xenografts in Lewis rats.
Lewis rats were used as recipients of hamster heart or liver grafts using different regimens of FK506 and Lef. Donor-matched heart grafts were transplanted into long-term surviving Lewis rat recipients of hamster xenografts to test donor-specific prolongation of xenograft survival. Hyperimmune, late xenograft rejection, and naive sera were transferred into long-term surviving Lewis rat recipients of hamster heart xenografts to determine whether these sera could inhibit the efficacy of donor-specific long-term survival. Anti-donor-specific antibodies were analyzed by flow cytometry.
After a short induction with FK506 plus Lef, maintenance treatment with FK506 alone was sufficient to prolong survival of hamster xenografts. All hamster heart and four of six hamster liver xenografts survived for more than 3 months. Second hamster hearts were permanently accepted by Lewis rats bearing long-term surviving hamster heart xenografts when rats were treated with FK506 monotherapy (mean survival time >60 days, n=4). Long-term surviving hamster heart grafts were rejected after transfer of hyperimmune serum but not late xenograft rejection serum or naive serum. Lef and FK506 significantly reduced the production of anti-donor-specific antibodies in Lewis rats transplanted with hamster liver and heart xenografts.
Long-term survival of hamster liver and heart xenografts in Lewis rats could be induced by a regimen of short-term FK506 in combination with Lef followed by FK506 monotherapy. The acquired sensitivity of late xenoreactivity to FK506 reflects primarily a modification in the host immune response to the hamster graft.
在本实验中，我们研究了免疫抑制剂FK506和来氟米特（Lef）对仓鼠心脏和肝脏异种移植物在Lewis大鼠体内存活的影响。
使用不同方案的FK506和Lef，将Lewis大鼠作为仓鼠心脏或肝脏移植物的受体。将供体匹配的心脏移植物移植到长期存活的仓鼠异种移植Lewis大鼠受体中，以测试异种移植物存活的供体特异性延长情况。将超免疫、晚期异种移植排斥和未免疫血清转移到长期存活的仓鼠心脏异种移植Lewis大鼠受体中，以确定这些血清是否能抑制供体特异性长期存活的效果。通过流式细胞术分析抗供体特异性抗体。
用FK506加Lef进行短期诱导后，单独使用FK506维持治疗足以延长仓鼠异种移植物的存活时间。所有仓鼠心脏和六只仓鼠肝脏异种移植物中的四只存活超过3个月。当用FK506单一疗法治疗大鼠时，第二个仓鼠心脏被长期存活的仓鼠心脏异种移植Lewis大鼠永久接受（平均存活时间>60天，n = 4）。长期存活的仓鼠心脏移植物在转移超免疫血清后被排斥，但晚期异种移植排斥血清或未免疫血清则不会。Lef和FK506显著降低了移植仓鼠肝脏和心脏异种移植物的Lewis大鼠体内抗供体特异性抗体的产生。
短期FK506联合Lef然后FK506单一疗法的方案可诱导仓鼠肝脏和心脏异种移植物在Lewis大鼠体内长期存活。晚期异种反应性对FK506获得性敏感性主要反映了宿主对仓鼠移植物免疫反应的改变。
