Pathogenesis of vascular injury in rejecting rat renal allografts.
Unmodified rejection of rat renal allografts was characterized by the early onset and rapid progression of endothelial damage in venules and capillaries which culminated in ischemic cortical necrosis. This pattern of endothelial injury correlated with lymphocyte accumulation in vascular lumens and could not be duplicated by renal perfusion with alloantibodies or prevented by C'3 depletion. In contrast, endothelial integrity and normal graft function were maintained over study intervals extending to 200 days when Brown Norway (BN) rat kidneys were transplanted into Lewis (Le) rat kidney recipients subjected to neonatal thymectomy or lymph drainage. Vascular lesions occurred when syngeneic thoracic duct lymphocytes were transfused into these recipients, but irreversible endothelial injury could be prevented by simultaneous injections of immune plasma. These findings indicate that the destruction of donor endothelium is mediated by thymus-dependent immune mechanisms which can be altered by thoracic duct drainage to promote indefinite survival of renal allografts across major histocompatibility loci.
D000818:Animals; D003176:Complement C3; D004322:Drainage; D004727:Endothelium / Q000098:blood supply; D005455:Fluorescent Antibody Technique; D006084:Graft Rejection; D006085:Graft Survival; D006087:Graft vs Host Reaction; D007109:Immunity; D007511:Ischemia / Q000209:etiology; D007518:Isoantibodies; D007672:Kidney Cortex / Q000098:blood supply; D007673:Kidney Cortex Necrosis / Q000209:etiology*; D016030:Kidney Transplantation; D008212:Lymphocyte Depletion; D011183:Postoperative Complications; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology; D013897:Thoracic Duct / Q000601:surgery; D013934:Thymectomy; D014184:Transplantation, Homologous / Q000379:methods
D003176:Complement C3; D007518:Isoantibodies