Rapaport F T, Bachvaroff R J, Mollen N, Hirasawa H, Asano T, Ferrebee J W
Ann Surg. 1979 Oct;190(4):461-73. doi: 10.1097/00000658-197910000-00006.
Transplantation of renal allografts obtained from prospectively selected genotypically DLA-identical donors into supralethally irradiated dogs reconstituted with their own stored bone marrow has produced a state of unresponsiveness to these kidneys in the recipients. Eleven of 18 kidneys transplanted at 12 hours after marrow replacement currently survive with normal function and maintain life in the recipients for 757, 800, 825, 978, 1062, 1092, 1136, 1282, 1373, 1380, and 1381 days, respectively. Similar results occurred in eight of 13 allografts transplanted at 28 hours after marrow replacement, which currently survive for 349, 363, 377, 407,436,470, 485, and 513 days, respectively, and in eight of 13 kidneys grafted at 36 hours after marrow replacement, which are surviving for 197, 247, 298, 324, 337, 396, 443, and 472 days, respectively. Achievement of optimal results is dependent on the specific timing and sequence of each procedure. Only four of 16 recipients of kidneys transplanted at the time of marrow replacement were unresponsive to their allografts. Similarly, only five of 19 recipients of kidneys placed in irradiated dogs at 40 hours before marrow replacement accepted such allografts. When kidney transplants were placed into the recipients 20 hours before removal of marrow, irradiation, and reconstitution with stored marrow, only three of 21 dogs became unresponsive to such ailografts. In five of 12 instances, the recipients were also unresponsive to skin allografts obtained from their respective kidney donors. Such skin grafts currently survive for 606, 673, 687, 701, and 708 days, respectively. The remaining seven skin grafts were rejected at 28, 39,42, 84, 90, 92, and 115 days, respectively. Second- and third-set skin grafts from the same kidney donor were rejected by six of these dogs at 19, 20, 21, 29, 29, and 30 days, and at 21, 22, 23, 24, 27, and 27 days, respectively. Rejection of these skin grafts had no detectable effect on the function and survival of kidney allografts from the same source. Seven of eight skin grafts obtained from other DLA-identical donors were rejected at 13,14,16,25,28,38, and 84 days, respectively; one allograft continues to survive for 708 days. Eleven DLA-incompatible skin allografts placed on the recipients at the same time were rejected within 11-20 days. Supralethal total body irradiation and bone marrow replacement can establish in the adult canine host a privileged phase of immunological reactivity during which exposure to alloantigens produces specific long-term unresponsiveness rather than sensitization. The use of stored autologous rather than allogeneic bone marrow for reconstitution of the irradiated recipient eliminates the hazards of GVH complication usually associated with this procedure. This consideration and the apparent capacity of the tolerant host to maintain a long-term state of unresponsiveness without any further immunosuppressive therapy point to the potential relevance of the results to human transplantation.
将前瞻性选择的基因分型DLA相同供体的同种异体肾移植到经超致死剂量照射并用自身储存骨髓重建的犬体内，可使受体对这些肾脏产生无反应状态。在骨髓置换后12小时移植的18个肾脏中，有11个目前功能正常存活，分别维持受体生命757、800、825、978、1062、1092、1136、1282、1373、1380和1381天。在骨髓置换后28小时移植的13个同种异体肾中有8个也出现了类似结果，目前分别存活349、363、377、407、436、470、485和513天；在骨髓置换后36小时移植的13个肾脏中有8个存活，目前分别存活197、247、298、324、337、396、443和472天。取得最佳结果取决于每个程序的具体时间和顺序。在骨髓置换时移植肾脏的16个受体中只有4个对其同种异体肾无反应。同样，在骨髓置换前40小时将肾脏植入受照射犬体内的19个受体中只有5个接受了这种同种异体肾。当在去除骨髓、照射并用储存骨髓重建前20小时将肾移植植入受体时，21只犬中只有3只对这种同种异体肾无反应。在12例中有5例，受体对从各自肾供体获得的皮肤同种异体移植也无反应。这种皮肤移植目前分别存活606、673、687、701和708天。其余7个皮肤移植分别在28、39、42、84、90、92和115天被排斥。来自同一肾供体的第二组和第三组皮肤移植被其中6只犬分别在19、20、21、29、29和30天以及21、22、23、24、27和27天排斥。这些皮肤移植的排斥对来自同一来源的同种异体肾的功能和存活没有可检测到的影响。从其他DLA相同供体获得的8个皮肤移植中有7个分别在13、14、16、25、28、38和84天被排斥；一个同种异体移植继续存活708天。同时放置在受体身上的11个DLA不相容皮肤同种异体移植在11 - 20天内被排斥。超致死剂量全身照射和骨髓置换可在成年犬宿主中建立一个免疫反应特权阶段，在此期间接触同种异体抗原会产生特异性长期无反应而不是致敏。使用储存的自体骨髓而不是同种异体骨髓来重建受照射受体可消除通常与此程序相关的移植物抗宿主并发症的风险。这一考虑以及耐受宿主在无需任何进一步免疫抑制治疗的情况下维持长期无反应状态的明显能力表明这些结果与人类移植可能相关。
