Yamada K, Choo J K, Allan J S, Erhorn A E, Menard M T, Mawulawde K, Slisz J K, Aretz H T, Shimizu A, Sachs D H, Madsen J C
Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Transplantation. 1999 Aug 27;68(4):485-91. doi: 10.1097/00007890-199908270-00007.
We have previously demonstrated that MHC class I disparate hearts transplanted into miniature swine treated with a short course of cyclosporine developed florid cardiac allograft vasculopathy (CAV) and were rejected within 55 days. However, when a donor-specific kidney is cotransplanted with the heart allograft, recipients become tolerant to donor antigen and accept both allografts long-term without the development of CAV. In the present study, we have investigated the role of the host thymus in the induction of tolerance and prevention of CAV in heart/kidney recipients.
Total thymectomies were performed in six animals (postoperative day [POD]-21), which on day 0 received either an isolated MHC class I disparate heart allograft (n=3) or combined class I disparate heart and kidney allografts (n=3), followed in both cases by a 12-day course of cyclosporine (POD 0-11). Graft survival and the development of CAV in these thymectomized recipients were compared to the same parameters in non-thymectomized, cyclosporine-treated recipients bearing either class I disparate heart allografts (n=5) or heart and kidney allografts (n=4).
In the group of animals bearing isolated class I disparate heart allografts, the thymectomized recipients rejected their allografts earlier (POD 8, 22, 27) than the non-thymectomized recipients (POD 33,35,45,47,55). The donor hearts in both the thymectomized and non-thymectomized animals developed florid CAV. In the group of animals bearing combined class I disparate heart and kidney allografts, the nonthymectomized recipients accepted both donor organs long term with no evidence of CAV. In contrast, none of the thymectomized heart/kidney recipients survived >100 days, and they all developed the intimal proliferation of CAV.
Thymic-dependent mechanisms are necessary for the induction of acquired tolerance and prevention of CAV in porcine heart/kidney recipients.
我们之前已经证明，将主要组织相容性复合体（MHC）I类不相容的心脏移植到接受短期环孢素治疗的小型猪体内，会出现严重的心脏移植血管病变（CAV），并在55天内被排斥。然而，当将供体特异性肾脏与心脏同种异体移植物共同移植时，受体对供体抗原产生耐受，并长期接受这两种同种异体移植物，且不会发生CAV。在本研究中，我们调查了宿主胸腺在心脏/肾脏受体耐受诱导和CAV预防中的作用。
对6只动物进行全胸腺切除术（术后第[POD]-21天），这些动物在第0天接受了单独的MHC I类不相容心脏同种异体移植（n=3）或I类不相容心脏和肾脏联合同种异体移植（n=3），随后在两种情况下均接受为期12天的环孢素治疗（POD 0-11）。将这些胸腺切除受体的移植物存活情况和CAV的发生情况与未进行胸腺切除、接受环孢素治疗的受体（分别接受I类不相容心脏同种异体移植，n=5；或心脏和肾脏同种异体移植，n=4）的相同参数进行比较。
在接受单独的I类不相容心脏同种异体移植的动物组中，胸腺切除受体比未进行胸腺切除的受体更早地排斥了它们的同种异体移植物（POD 8、22、27）（POD 33、35、45、47、55）。胸腺切除和未进行胸腺切除的动物的供体心脏均出现了严重的CAV。在接受I类不相容心脏和肾脏联合同种异体移植的动物组中，未进行胸腺切除的受体长期接受了两个供体器官，且没有CAV的迹象。相比之下，没有一只胸腺切除的心脏/肾脏受体存活超过100天，并且它们都出现了CAV的内膜增生。
胸腺依赖机制对于诱导猪心脏/肾脏受体获得性耐受和预防CAV是必要的。
