Chronic rejection (CR) is the most common cause of late graft failure after solid organ transplantation. To assess the mechanisms of induction and expression of this important process, a new model of CR was developed in the mouse.

A 1cm segment of donor thoracic aorta was used to replace a section of recipient abdominal aorta below the renal arteries and above the aortic bifurcation. Initial mortality was 70% but changes in technique resulted in a high rate of success (75%). Mice developed the intimal proliferative lesion of CR by 8 wk post transplantation.

In a comparative study, vessels in human tissue sections from chronically rejected renal allografts were compared to mouse and rat aortic allograft specimens. Both human and mouse developed concentric intimal lesions with 100% of the circumference of the vessel involved. In the rat, the lesion was eccentric with a mean of 49% of the circumference involved. This suggests the process in the mouse may more closely resemble that in human CR.

In examining the relative contributions of MHC and mH to the development of chronic rejection, I found that MHC identity in the face of mH disparity did not prevent or ameliorate chronic rejection. The intimal lesion was associated with an increase in the smooth muscle cell component and medial atrophy.

This new model of chronic rejection which develops a lesion similar to that seen in human chronic rejection, has been used to demonstrate that MHC matching alone will not prevent chronic rejection. It has powerful potential to unlock the mystery of the mechanism of graft arteriosclerosis.