Overexpression of heme oxygenase-1 protects allogeneic thyroid grafts fromrejection in naive mice

Background. Endocrine allografts are an option for the treatment of endocri ne failure. Methods. One lobe of the thyroid was transplanted tender the kidney capsule . Results, C57BL/10 (H2(b)) thyroids were rejected in naive CBA (H2(k) mice w ithin 14 days after transplantation. When mice were treated with anti-CD4 m onoclonal antibodies (mAb), all grafts survived for more than 60 days. The first grafts still survived after second C57BL/10 or Balb/c (H2(d)) thyroid grafts that were transplanted into same recipients were rejected acutely, which suggests that the primary grafts were modified under anti-CD4 mAb tre atment. To confirm this hypothesis, C57BL/10 thyroid grafts from anti-CD4 m Ab-treated mice were retransplanted. All grafts survived in naive mice; thi s correlated with the overexpression of heme oxygenase-1 (HO-1) in the graf ts Next, an inhibitor of HO-1 (zinc protoporphyrin) or control compound (co pper protoporphyrin) was injected intraperitoneally after transplantation o f C57BL/10 thyroid grafts into the primary CBA recipients that had been tre ated with anti-CD4 mAb. The grafts in mice that had been treated with zinc protoporphyrin, but not copper protoporphyrin, were rejected when retranspl anted to naive recipients. Conclusions. Overexpression of HO-1 correlated, with the protection of full y allogeneic thyroid grafts from rejection when retransplanted into naive r ecipients.