T lymphocytes mediate leaflet destruction and allograft aortic valve failure in rats

Abstract

Background. Allograft heart valves are commonly used in cardiac surgery but ultimately fail. This situation is most acute in children. This study addresses the role of T cell–mediated immune damage in allograft valve failure. Methods. Syngeneic (Lewis to Lewis) or allogeneic (Brown Norway to Lewis) aortic valve grafts were implanted infrarenally into Lewis rat recipients (n = 24). Allogeneic valve grafts were also implanted into T cell–deficient rats (nude; n = 12). At 7, 14, and 28 days the valves were explanted and examined for structural integrity and cellular infiltration. Results. Syngeneic grafts maintained normal leaflet structure with little leaflet immune infiltration. Allografts showed leaflet infiltration (7 days), significant leaflet thickening, progressively decreased cellularity (14 days), and leaflet destruction (28 days). Infiltrates contained CD43+, CD3+, and CD8+ cells. Allografts in T cell–deficient rats showed none of the above changes and maintained normal structural integrity. Conclusions. Allograft heart valves in the rat model undergo T cell–mediated immune rejection, resulting in structural failure.