Cellular and vascular components of the allograft reaction. Evidence from returned skin allografts.

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.