Mezrich Joshua D, Benjamin Louis C, Sachs Jessica A, Houser Stuart L, Vagefi Parsia A, Sachs David H, Madsen Joren C, Yamada Kazuhiko
Transplantation Biology Research Center, Massachusetts General Hospital-Harvard Medical School, 13th Street, Boston, MA, USA.
Transplantation. 2005 Jun 27;79(12):1663-73. doi: 10.1097/01.tp.0000160679.04441.b7.
The authors have examined the mechanism whereby co-transplantation of a kidney and heart from the same donor induces and maintains tolerance to both organs in miniature swine.
Transplants were performed across a major histocompatibility complex class I mismatch, and recipients received cyclosporine for 12 days. Group 1 animals received heart transplants alone (n=5), and all other groups received both heart and kidney allografts. Group 2 animals received no further intervention (n=2). Group 3 animals underwent transplant nephrectomy 8 days after heart and kidney co-transplantation (n=2). Group 4 animals underwent transplant nephrectomy 100 days after co-transplantation (n=2). Skin grafts were placed on group 4 animals, on one group 3 animal, and on two animals from group 2. Group 5 animals underwent thymectomy 100 days after co-transplantation (n=4).
Group 1 animals developed cardiac allograft vasculopathy (CAV) and rejection. Group 2 animals never developed CAV and demonstrated in vitro donor-specific unresponsiveness. Group 3 animals suffered CAV and rejection. Group 4 animals developed CAV without concomitant donor-specific cell-mediated lympholysis reactivity, interstitial rejection, or cessation of graft function. Skin grafts on group 3 and group 4 animals led to fulminant rejection of heart and skin grafts, in contrast to grafts on group 2 animals that had no in vivo effect. Group 5 animals developed CAV but no significant increase in interstitial infiltrates.
Both the kidney and thymus were necessary for maintenance of tolerance to heart allografts.
作者研究了同一供体的肾脏和心脏联合移植诱导并维持小型猪对这两个器官耐受性的机制。
移植手术跨越主要组织相容性复合体I类不匹配，受体接受环孢素治疗12天。第1组动物仅接受心脏移植（n = 5），所有其他组接受心脏和肾脏同种异体移植。第2组动物未接受进一步干预（n = 2）。第3组动物在心脏和肾脏联合移植后8天接受移植肾切除术（n = 2）。第4组动物在联合移植后100天接受移植肾切除术（n = 2）。将皮肤移植物移植到第4组动物、1只第3组动物和2只第2组动物身上。第5组动物在联合移植后100天接受胸腺切除术（n = 4）。
第1组动物发生心脏同种异体移植血管病变（CAV）和排斥反应。第2组动物从未发生CAV，并表现出体外供体特异性无反应性。第3组动物遭受CAV和排斥反应。第4组动物发生CAV，但未伴随供体特异性细胞介导的淋巴细胞溶解反应性、间质排斥反应或移植功能停止。第3组和第4组动物的皮肤移植物导致心脏和皮肤移植物的暴发性排斥反应，相比之下，第2组动物的移植物在体内没有影响。第5组动物发生CAV，但间质浸润没有显著增加。
肾脏和胸腺对于维持心脏同种异体移植的耐受性都是必需的。
