PRESENSITIZATION ACCELERATES ALLOGRAFT ARTERIOSCLEROSIS

Transplant arteriosclerosis is the major factor influencing allograft survival after the first year posttransplantation, The host's immunolo gic response is one of the principal effecters responsible for the con stitution of this vascular wall lesion, but the effector pathway and t he factors influencing the immune injury are not clear, In a rat abdom inal aortic allograft model, we used a skin priming method to study th e influence of sensitization on the occurence of vascular wall lesions . Primed rats developed transplant arteriosclerosis lesions involving medial decellularization and intimal proliferation before the 21st day , whereas naive animals had the same lesions at 2 months posttransplan tation. A significant difference between primed and naive rats was fou nd for medial thickness (48.00+/-2.85 mu m versus 79.34+/-2.55 mu m, P <0.001) and smooth muscle cell content (160+/-28 cell/mm versus 466+/- 19 cell/mm, P<0.001) at 21 days posttransplantation, and intimal hyper plasia was seen in primed animals at that time, whereas it was not obs erved in naive rats until the 60th day. The immune profile in naive an d primed animals was different, The immune cells infiltrating the arte rial wall in naive rats, were principally macrophages and CD8+ T-lymph ocytes. No Ig or complement deposition was detected, IgG and complemen t activated fraction were present in the media of primed animals as ea rly as the fifth day posttransplantation and CD4+ T lymphocytes were t he dominant immune cell population. In conclusion, sensitization influ ences the immune mechanisms responsible for the development of transpl ant arteriosclerosis and alters the rate of its evolution.