Madariaga M L, Michel S G, La Muraglia G M, Sekijima M, Villani V, Leonard D A, Powell H J, Kurtz J M, Farkash E A, Colvin R B, Allan J S, Cetrulo C L, Huang C A, Sachs D H, Yamada K, Madsen J C
Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
Department of Cardiac Surgery, Ludwig-Maximilians-Universität, Munich, Germany.
Am J Transplant. 2015 Jun;15(6):1580-90. doi: 10.1111/ajt.13131. Epub 2015 Mar 30.
Kidney allografts possess the ability to enable a short course of immunosuppression to induce tolerance of themselves and of cardiac allografts across a full-MHC barrier in miniature swine. However, the renal element(s) responsible for kidney-induced cardiac allograft tolerance (KICAT) are unknown. Here we investigated whether MHC disparities between parenchyma versus hematopoietic-derived "passenger" cells of the heart and kidney allografts affected KICAT. Heart and kidney allografts were co-transplanted into MHC-mismatched recipients treated with high-dose tacrolimus for 12 days. Group 1 animals (n = 3) received kidney and heart allografts fully MHC-mismatched to each other and to the recipient. Group 2 animals (n = 3) received kidney and heart allografts MHC-matched to each other but MHC-mismatched to the recipient. Group 3 animals (n = 3) received chimeric kidney allografts whose parenchyma was MHC-mismatched to the donor heart. Group 4 animals (n = 3) received chimeric kidney allografts whose passenger leukocytes were MHC-mismatched to the donor heart. Five of six heart allografts in Groups 1 and 3 rejected <40 days. In contrast, heart allografts in Groups 2 and 4 survived >150 days without rejection (p < 0.05). These data demonstrate that KICAT requires MHC-matching between kidney allograft parenchyma and heart allografts, suggesting that cells intrinsic to the kidney enable cardiac allograft tolerance.
肾移植能够在小型猪中实现短期免疫抑制，从而诱导对自身以及跨越完全主要组织相容性复合体（MHC）屏障的心脏移植产生耐受性。然而，负责肾脏诱导的心脏移植耐受性（KICAT）的肾脏因素尚不清楚。在此，我们研究了心脏和肾脏移植的实质细胞与造血来源的“过客”细胞之间的MHC差异是否会影响KICAT。将心脏和肾脏移植共同移植到接受高剂量他克莫司治疗12天的MHC不匹配受体中。第1组动物（n = 3）接受的肾脏和心脏移植彼此之间以及与受体的MHC完全不匹配。第2组动物（n = 3）接受的肾脏和心脏移植彼此MHC匹配，但与受体MHC不匹配。第3组动物（n = 3）接受嵌合肾移植，其实质与供体心脏的MHC不匹配。第4组动物（n = 3）接受嵌合肾移植，其过客白细胞与供体心脏的MHC不匹配。第1组和第3组中六分之五的心脏移植在40天内发生排斥反应。相比之下，第2组和第4组的心脏移植存活超过150天且未发生排斥反应（p < 0.05）。这些数据表明，KICAT需要肾移植实质与心脏移植之间的MHC匹配，这表明肾脏固有的细胞能够实现心脏移植耐受性。
