Clinical course, morphology, and treatment of chronically rejecting small bowel allografts

As acute rejection episodes are most frequently prevented or controlled in clinical organ transplantation, chronic rejection processes have become the major reason for late dysfunction and eventual loss of the allograft. The recent reports on successful clinical intestinal transplantation prompted us to investigate chronic rejection processes that may arise after the initial control of acute rejection. Using the strongly histoincompatible ACI-->LEW rat strain combination and serial graft biopsies after limited initial immunosuppressive therapy with cyclosporine, we defined the clinical and pathomorphologic course of chronic rejection of orthotopic small bowel allografts. Differing from acute rejection, the bowel wall (especially the mucosa and submucosa) was not the primary target of chronic rejection. We observed progressive destruction of the Peyer's patches and the mesenteric lymph nodes of the graft--a process which began during the 4-week course of CsA--and infiltration and destruction of graft mesenteric vessels. Testing the immunosuppressive drugs FK506 and CsA for their efficacy to ameliorate ongoing chronic rejection, we found that a short course (5 days) of FK506 was more effective than a second 4-week course of CsA. However, while allograft function recovered sufficiently to allow a temporary improvement of the recipient's global nutritional state, pathomorphologic graft changes failed to reverse substantially. Eventually all grafts failed due to progressive chronic rejection.