The Efficacy of Intrathymic Immune Modulation After Allogeneic Tissue Transplantation (Skin and Neonatal Heart) in the Rat

To date, transplant arteriosclerosis (TA), the histologic counterpart of chronic transplant dysfunction, is the most important problem in clinical organ transplantation. Recently we showed in rats that intrathymic (IT) immune modulation substantially prolonged graft survival of MHC-incompatible, heterotopic vascularized cardiac allografts. Although acute rejection was prevented, eventually TA was found to develop. In this study, we analyzed the efficacy of IT immune modulation in two other, more simple, transplant models in which we transplanted tissues instead of whole organs: allogeneic skin transplantation and allogeneic neonatal heart-in-ear transplantation. Results indicate that IT immune modulation does not prolong graft survival of allogeneic skin grafts. Tissue specific antigens present on the skin grafts may account for this. Graft survival of neonatal cardiac allografts transplanted subcutaneously in the ear-pinnae of recipient rats was significantly prolonged following IT immune modulation. In long-term surviving neonatal allografts, neo-angiogenesis of graft myocardial tissue was observed which was characterized by the appearance of cavernouslike vascular structures. IT immune modulation is effective in inducing prolonged graft survival after allogeneic cardiac tissue transplantation, whereas graft survival of allogeneic skin grafts is not prolonged. In contrast to vascularized cardiac allografts, development of TA was not observed in transplanted neonatal heart tissue, most probably as a result of lack of appropriate vascular structures (functional coronary arteries).