No abstract

These results demonstrate that monotherapy with clopidogrel can effectively reduce the formation of transplant arteriosclerosis in a murine aortic allograft model.

This report shows that application of clopidogrel after transplantation results in a reduction in adhesion molecule expression within the blood and transplant tissue and is associated with reduced transendothelial migration of dendritic cells and macrophages within the vascular wall.

Summary Experimental and clinical data provide evidence that TNF‐α contributes to acute and chronic allograft rejection. In this study, we explored the effect of TNF‐α blockade using the chimeric monoclonal antibody infliximab on the development of transplant arterisoclerosis in a fully mismatched aortic allograft model. Post‐transplant treatment of CBA (H2k) recipients with 250 μg infliximab (cumulative dose 1.25 mg) reduced luminal occlusion of C57Bl/6 (H2b) aortic grafts on day 30 from 77 ± 5% in untreated controls to 52 ± 6%. Increasing the dose of anti‐TNF‐α antibody had no further beneficial effect. Treatment with human control immunoglobulin had no effect on intima proliferation. Under TNF‐α blockade, ICAM‐1 and PDGF mRNA expression within the grafts was strongly reduced, whereas iNOS expression was enhanced. The data show that TNF‐α blockade using infliximab can reduce the development of transplant arteriosclerosis in fully mismatched murine aortic grafts.

These data suggest that although alloantigen presentation in secondary lymphoid organs is hampered in CCR7-deficient recipients, this process may take place within the allograft itself, leading to increased formation of transplant arteriosclerosis. The decrease in Foxp3 expression despite increased in CD4 T cell infiltration indicates a reduction in T regulatory cells possibly influencing the intensity of the graft rejection.