Prolonged skin allograft survival through enhancement effects on donor tissue

A skin allograft retransplantation model was utilized to study the mechanism of immunological enhancement in a murine system. Enhancement was accomplished by treating allografted recipients with host antidonor serum (B6AF1 anti-B10.D2 alloantiserum). Grafts from enhanced or untreated hosts were retransplanted after seven days onto a second recipient. Enhanced retransplanted grafts had significantly prolonged survival as compared with unenhanced grafts. The survival of enhanced retransplanted grafts was as prolonged as that of primary skin grafts on antiserum-treated hosts. Splenocytes harvested from recipients of enhanced retransplanted allografts showed delayed and diminished development of T cell responses to graft alloantigens. Sensitization of the second recipient abrogated prolonged survival of enhanced retransplanted grafts. Also, enhancement prevented sensitization of allografted recipients. One interpretation of these studies suggests that a sensitization block is a sufficient mechanism of skin allograft enhancement. The site of action of antisera is within the graft itself. Decreased T cell responses in the host are indirect effects of diminished antigenicity of enhanced grafts. Further studies of immunological enhancement should be directed to the graft, not toward the graft recipient.