Estradiol inhibits allograft-inducible major histocompatibility complex class II antigen expression and transplant arteriosclerosis in the absence ofimmunosuppression

Background. The etiology of transplant arteriosclerosisis unknown, but curr ent data point to the alloimmune response. Previously, we found that estrad iol-17 beta (E2) with immunosuppressant cyclosporine abolishes major histoc ompatibility complex (MHC) class II expression in the allograft. This study determines the effect of E2 on MHC class II: antigen expression in the all ograft, in the absence of immunosuppression. Methods. Lewis male rats received orthotopic abdominal aorta allografts fro m male Brown-Norway rats. The recipients were treated continuously subcutan eously with either 20 mu g kg(-1).day(1) of E2 (n=20) dr placebo (n=20), fr om 2 days before transplantation until death on posttransplant days 1, 3, 7 , and 14. The allografts were harvested and processed for morphometry and f or immunohistochemical staining of MHC class II antigens, macrophages, CD4 and CDS T lymphocytes, interferon-gamma (IFN-gamma), and IFN-gamma receptor . Results With E2 treatment, we observed that inducible MHC class II antigen expression is abolished in the media of the vascular allograft; the express ion of IFN-gamma and IFN-gamma receptor is unaffected; and macrophage infil tration of the vascular allograft is inhibited significantly (P<0.01), wher eas the CD4 and CD8 T lymphocytes are not significantly (P=0.07) suppressed . The myointimal hyperplasia in the allografts from E2-treated-recipients w as 3-4-fold less than that from the placebo-treated recipients. Conclusions. Without immunosuppression, E2 inhibition of transplant arterio sclerosis is still associated with inhibition of inducible MHC% class II an tigen expression in the allografts. The estradiol-17 beta abolition of indu cible MHC class II antigen expression in the aorta allograft occurs in spit e of up-regulation of IFN-gamma ligand and receptor protein.