Lambert P B, Frank H A
J Exp Med. 1970 Nov;132(5):868-84. doi: 10.1084/jem.132.5.868.
In order to gain added insight into the mechanisms of allograft destruction, skin grafts were returned to their original donors after remaining as allografts long enough to induce immunity in the intermediate host but not long enough to cause destruction of the graft. Upon their return to unmodified donors, such grafts became revascularized and remained viable. An intense cellular infiltration was incited within the graft and its draining lymph node by the interaction between immunologically competent cells, some antigenically activated, that were transferred from the intermediate host with the graft, and those of the final host, the original donor. This immune interaction excited a nonspecific granulocytic and histiocytic response, which led to the destruction of the adjacent epithelium already re-accepted within its native habitat. This mechanism of epithelial destruction required vascular connection to permit the cellular infiltration, and was unlikely to have primarily involved circulating antibody. When similar grafts were returned to donors that had been sensitized to the intermediate host, vascularization and reacceptance of the graft did not occur. No cellular infiltration took place in the graft and no lymph node response was evoked. The returned grafts were cast off as full-thickness sloughs. Here the mechanism of graft rejection was apparently an interaction between the preformed antibody of the specifically sensitized host and the allogeneic cells transferred from the intermediate host; this interaction prevented the vascularization of the graft, even though the endothelia involved were autologous. In unmodified allografts, both the character and the variability of the histologic patterns can be accounted for by the superimposition, in differing rates and degrees, of humoral vascular effects upon cellular events already in progress.
为了更深入地了解同种异体移植破坏的机制，皮肤移植在作为同种异体移植保留足够长的时间以在中间宿主中诱导免疫但又不足以导致移植物破坏后，被送回其原始供体。当它们回到未改变的供体时，这些移植物重新血管化并保持存活。从中间宿主与移植物一起转移的一些抗原激活的免疫活性细胞与最终宿主（原始供体）的细胞之间的相互作用，在移植物及其引流淋巴结内引发了强烈的细胞浸润。这种免疫相互作用激发了非特异性粒细胞和组织细胞反应，导致已经在其天然栖息地重新接受的相邻上皮细胞被破坏。这种上皮细胞破坏机制需要血管连接以允许细胞浸润，并且不太可能主要涉及循环抗体。当将类似的移植物送回对中间宿主致敏的供体时，移植物不会发生血管化和重新接受。移植物中没有发生细胞浸润，也没有引起淋巴结反应。送回的移植物作为全层脱落物被排出。在这里，移植物排斥的机制显然是特异性致敏宿主的预先形成的抗体与从中间宿主转移的同种异体细胞之间的相互作用；这种相互作用阻止了移植物的血管化，即使所涉及的内皮细胞是自体的。在未改变的同种异体移植物中，可以通过体液血管效应以不同的速率和程度叠加在已经进行的细胞事件上来解释组织学模式的特征和变异性。
