Acute Destruction by Humoral Antibody of Rat Skin Grafted to Mice

Abstract
Rat skin grafted onto mice whose immune responses had been suppressed by thymectomy and treatment with rabbit anti-mouse lymphocyte serum survived for 23 to 62 days. About 2 weeks after transplantation, when the grafts had become well vascularized and were in excellent condition, some of the recipients were injected with antiserum that had been made by injecting rat tissues into mice or rabbits. Signs of inflammation were evident in the grafts within 10 min after intravenous administration of mouse anti-rat serum. These consisted of edema and erythema which increased in intensity over the next few hours and were followed by hemorrhage and necrosis. Many of the grafts were completely destroyed at 24 hr and most of them had been sloughed by the end of the 2nd day. Microscopic examination of fixed tissues revealed the occurrence of edema and the margination of polymorphonuclear leukocytes as early as 5 to 10 min after injection of antiserum. These leukocytes rapidly increased in number and migrated into the interstitial spaces. Small vessels became greatly dilated and congested and fibrin thrombi became evident at 4 to 6 hr. At this time many vessels were ruptured, and hemorrhage was widespread. In a small percentage of cases the grafts recovered from the early inflammation and were actively rejected by their hosts 2 to 10 weeks later. The reactions observed after injections of antiserum intraperitoneally were essentially the same as those described above, but they began later and developed more slowly in the early stages. Both macroscopic and microscopic features of these reactions induced by anti-rat serum were similar to those described for Arthus reactions and other forms of immune vasculitis. Rabbit anti-rat serum also caused destruction of rat skin that had been grafted onto mice, suggesting that this experimental system may be useful in studying the effects of different antisera on tissues from a variety of species.