REDUCED TRANSPLANT ARTERIOSCLEROSIS IN MURINE CARDIAC ALLOGRAFTS PLACED IN INTERFERON-GAMMA KNOCKOUT RECIPIENTS

To investigate the functional role of interferon (IFN)-gamma in transp lant arteriosclerosis, BALB/c hearts were transplanted in immunosuppre ssed C57BL/6J recipients with (n = 10) or without (n = 10) targeted IF N-gamma gene deletion. In 55-day heart allografts, IFN-gamma deficienc y resulted in a significant decrease in vascular thickening. The sever ity of intimal thickening measured as the percentage of luminal occlus ion (mean +/- SEM) in all elastin stained vessels (n = 410) decreased from 37 +/- 5% in wild-type recipients to 18 +/- 5% in IFN-gamma -/- r ecipients (P < 0.005). In the few diseased vessels in grafts from IFN- gamma -/- recipients, the neointima was more cellular with a 90% incre ase in the nuclear density. This finding correlated with a 50% reducti on in fibrosis estimated by alpha-smooth muscle actin cell accumulatio n in the neointima. The reduction in severity and altered composition of vascular thickening in grafts from IFN-gamma -/- recipients shows t hat IFN-gamma contributes to arteriosclerotic development following tr ansplantation.