Antidonor humoral transfer induces transplant arteriosclerosis in aortic and cardiac graft models in rats

Objective: The humoral pathway is suggested as playing a key role in transplant arteriosclerosis. The humoral immunity is demonstrated in the present study to induce direct vascular lesion. Methods: Ten abdominal aortic grafts were performed on 4 groups of rats: Brown Norway ( BN) isografts, BN to Lewis ( LEW) allografts, and two BN to nude ( RNU) grafted groups with and without any humoral transfer. The humoral sera were obtained by skin grafts performed in BN to LEW combination. Lewis anti-BN alloantisera was transferred in nude recipients through intraperitoneal injections. The aortic wall was histologically studied with morphometric analysis on the 21st day. Two additional BN to RNU aortic graft groups were evaluated by immunohistochemistry on days 3 ( 10 rats) and 10 ( 10 rats). Results: In the absence of the humoral transfer, the BN aortic wall implanted in RNU remained intact. The humoral transfer induced a marked intimal proliferation ( 63 +/- 4 vs 4 +/- 1.1 mu m; P < .001) and an adventitial cell infiltration ( 5.1 +/- 0.7 vs 2.8 +/- 0.6 x 10(3) c/mm(2), P < .001). The medial thickness and the medial cell density were not modified. On day 3, the remaining endothelial cells were covered by immunoglobulin G deposits. On day 10 the endothelial cells disappeared completely and intimal proliferation occurred. In an additional cardiac graft group, transplant coronary arteriopathy was evidenced in 7 of the 9 nude recipients that had undergone the humoral transfer. Conclusion: The transplant arterial occlusive lesion is demonstrated here ( 1) to be induced by humoral antidonor immunity and ( 2) to be linked to an adventitial or perivascular inflammation.