Biological Factors in Tissue Transplantation

IN I804 Baronio clearly demonstrated that experimental free skin autografts in a sheep would survive. The wide variety of free autografts now used in plastic surgery are ample testimony to his findings. Skin grafts exchanged between identical twins were first shown to survive by Bauer in I927. Tissue transplants between members of highly inbred mouse strains are similarly accepted. A kidney that is removed and transplanted into the same individual, or his identical twin, will function almost as efficiently as before it was disturbed and can alone maintain the life of the organism for a period of years (Murray, Merrill and Harrison, 1958). Thus where genetic differences between graft and recipient can be excluded, technical considerations are the only important factors that determine the survival of transplanted tissue and although technical difficulties might be considerable, they are for the most part understood. In the present century in almost every branch of surgery, technical progress has resulted in successful exploitation of tissue transplantation within the same individual, either free, or with a partially intact blood supply. However, although these developments have been of great value, they have distinct limitations as to the source of the donor tissue. Thus if vital organs such as kidneys are irreversibly diseased or if an excessive amount of skin is burnt, the patient cannot supply the deficient tissue and surgery has little to offer him, unless he is fortunate enough to possess an identical twin. Jensen in 1903 showed that certain spontaneous tumours in mice could be transplanted and would continue to grow within some strains of inbred mice, but if the tumours were transplanted to individuals of another strain they would grow for a period and then be rejected. After rejection, if the same tumour source was transplanted to the same recipient a second time, it would not now survive even temporarily. These observations were the first demonstration of immunity to homologous tissue, although originally they were thought to represent properties of neoplastic as opposed to normal tissue. In I9II, Lexer, having made a study of skin grafts, stated categorically that skin homografts never take permanently. Holman in 1924 showed that a second skin homograft from the same donor to the same recipient was more rapidly rejected than the first. Confirmation and amplification of these findings were the first subject of the classical studies of Medawar and his associates (Gibson and Medawar, I943; Medawar, 1944, I945; Billingham, Brent, Medawar and Sparrow, 1954). The observation of these basic facts of homotransplantation, that were generally applicable to all vertebrate species studied, far from solving any of the problems, merely defined the field for investigation as follows: i. What genetic factors are concerned in the rejection of homologous tissue ? 2. How is grafted tissue destroyed ? 3. What is the mechanism of the heightened specific immunity that follows rejection of the first graft ?