EVIDENCE THAT RECIPIENT CD8(-CELL DEPLETION DOES NOT ALTER DEVELOPMENT OF CHRONIC VASCULAR REJECTION IN A RAT-HEART ALLOGRAFT MODEL() T)

Progressive chronic vascular rejection is a central feature of indefin itely surviving WF.1L LEW/Gut (RT1(1)) heart graft transplanted to LEW (RT1(1)) recipients in unmodified donor-recipient combinations. At 70 days posttransplantation, large vessels of the grafts are characteriz ed by the presence of vasculitis, vasculitis with associated variable myointimal thickening, and occlusive myointimal thickening with minima l or absent concomitant vasculitis. To assess the potential role of CD 8(+) T cells as critical effecters of chronic vascular rejection in th is model, LEW recipients of WF.1L heart grafts were effectively deplet ed of CD8(+) T cells as a result of prior thymectomy and anti-CD8 (MRC OX8) monoclonal antibody administration prior to transplantation. WF. 1L heart grafts transplanted to LEW recipients that had undergone prio r sham thymectomy and MRC OX8 administration, or thymectomy and admini stration of antibody-free culture supernatant, provided appropriate co ntrols. At 70 days posttransplantation, large vessels of WF.1L heart g rafts in all 3 transplantation groups showed similar morphologic featu res, which were comparable to those observed in heart grafts of long-s urviving unmodified donor-recipient pairs. This study has shown that p rofound selective depression of recipient CD8(+) T cells does not alte r the characteristic features of chronic vascular rejection in this ra t cardiac model, and provides evidence that CD8(+) T cells play no cri tical role in the initiation or development of progressive vascular da mage in this setting.