Factors responsible for the differential survival of heart and skin allografts in inbred rats.

It is common observation that orthotopic skin allografts are rejected acutely across certain histoincompatibility barriers in which surgically anastomosed hearts often survive for many months. In three normal or treated rat strain combinations that exhibit this pattern, neonatal heart tissue grafted in a free manner analogous to skin grafting (requiring natural vascularization, ischemic stress etc.) was also found to be rejected acutely. Consequently the differential survival of surgically anastomosed heart and skin allografts seems due to differences in the mode of grafting these tissues and not to different tissue specific antigens or inherent differential vulnerability of skin and heart. In addition the survival of these freely grafted heart as well as skin allografts were greatly extended when they were transplanted with surgically anastomosed hearts of the same inbred strain. This extension of survival appeared to result from the ability of surgically anastomosed hearts to induce unresponsiveness in their recipients. Subsequent experiments characterized this unresponsiveness as being immunological enhancement. Sera from heart organ allograft recipients passively enhanced the survival of freely grafted heart allografts. In addition, by the leucocyte migration test, lymph node cells and sera, respectively, from some of the heart recipients produced migration inhibition factor when exposed to antigen in culture and blocked production of the same.