Moller F, Hoyt G, Farfan F, Starnes V A, Clayberger C
Department of Cardiothoracic Surgery, Stanford University, California 94305.
Transplantation. 1993 Mar;55(3):650-5. doi: 10.1097/00007890-199303000-00034.
As the simultaneous transplantation of two or more organs into a single recipient has become increasingly common, asynchronous allograft rejection has become an important clinical problem. To investigate the cellular and molecular mechanisms underlying differential organ rejection, we developed a rat model in which heart and lung allografts were transplanted sequentially. Heterotopic heart allografts transplanted into DA recipients from PVG donors survived indefinitely if the recipients were given a short course of rabbit antirat thymocyte globulin or cyclosporine at the time of transplantation. In contrast, orthotopic left lungs transplanted under the same conditions were rejected in ATG-treated recipients and accepted in most CsA-treated recipients. These animals were then given a second organ allograft from the same strain or a third party to assess whether they exhibited donor specific tolerance and whether the acceptance or rejection of the first allograft would influence the survival of the second transplant. Animals tolerized to a heart allograft with ATG rejected an orthotopic lung transplant from the same strain as the original allograft, whereas recipients treated with CsA at the time of their heart transplant accepted a subsequent lung graft. Surprisingly, animals treated with either ATG or CsA that had rejected a lung allograft accepted a subsequent heart transplant. Using limiting dilution analysis and adoptive transfer studies, we found that some recipients had developed suppressor cells while others demonstrated anergy. We conclude that major histocompatibility complex antigens as well as other antigens are involved in the differential rejection of heart and lung allografts.
随着将两个或更多器官同时移植到单个受者体内的情况日益普遍，异步同种异体移植排斥已成为一个重要的临床问题。为了研究不同器官排斥背后的细胞和分子机制，我们建立了一个大鼠模型，其中心脏和肺同种异体移植是顺序进行的。如果在移植时给受者短期使用兔抗大鼠胸腺细胞球蛋白或环孢素，将PVG供体的异位心脏同种异体移植到DA受者体内可长期存活。相比之下，在相同条件下移植的原位左肺在接受ATG治疗的受者中被排斥，而在大多数接受CsA治疗的受者中被接受。然后给这些动物进行来自同一品系或第三方的第二次器官同种异体移植，以评估它们是否表现出供体特异性耐受，以及第一次同种异体移植的接受或排斥是否会影响第二次移植的存活。用ATG诱导对心脏同种异体移植耐受的动物排斥来自与原始同种异体移植相同品系的原位肺移植，而在心脏移植时接受CsA治疗的受者接受随后的肺移植。令人惊讶的是，接受过ATG或CsA治疗且排斥过肺同种异体移植的动物接受了随后的心脏移植。通过有限稀释分析和过继转移研究，我们发现一些受者产生了抑制细胞，而另一些则表现出无反应性。我们得出结论，主要组织相容性复合体抗原以及其他抗原参与了心脏和肺同种异体移植的差异排斥。
