Studies in the transplantation of bone. V. The capacity of fresh and treated homografts of bone to evoke transplantation immunity. 1963.

Skin transplanted as a homograft from one animal to a genetically dissimilar animal of the same species is rejected after nine to twelve days, probably because of actively acquired immune reactions (Medawar 1944, 1945; Billingham, Brent and Medawar 1954; Billingham, Brent, Medawar and Sparrow 1954). The acquired resistance is termed either transplantation immunity (Billingham, Brent and Medawar l956a) or, when occurring after homologous transplants, homograft sensitivity (Lawrence 1959). Homograft sensitivity may be revealed in a number of different ways. The most usual test is to apply at a later date to that sensitised host, a second skin graft, either from the same donor or from another member of the same inbred strain. Induced sensitivity is manifested by the earlier rejection at five to six days of the second-set graft, compared with nine to twelve days for the first-set graft (Medawar 1944; Billingham, Brent and Medawar 1954). Other tissues may be used to sensitise a host, provided the tissue contains nucleated cells. Medawar ( 1946a) found that injections of homologous leucocytes, but not homologous red blood corpuscles, would evoke transplantation immunity in rabbits. Subsequently it was shown with inbred strains of mice that, whereas the injection of isolated nuclei prepared from spleen, thymus and kidney cells would each evoke sensitivity to donor tissue, the injection of concentrated suspensions of cytoplasm obtained from liver and kidney cells would not do so (Billingham et a!. l956a). These workers concluded that the substances responsible for inducing transplantation immunity reside principally in the nuclei of cells. Makinodan, Gengozian and Albright (1958) reached a similar conclusion using red marrow cells, and they produced evidence that the antigens evoking the immunity were principally in the nucleated red and white blood cells of the marrow. This conclusion has, however, been challenged by Santos, Cole and Garver (1959). The transplantation of fresh homologous cartilage does not apparently evoke sensitivity to donor tissue. Craigmyle (1958) found that the implantation into rabbits of two hundred milligrams of diced homologous cartilage from the same donor on two occasions did not usually elicit transplantation immunity. Peacock, Weeks and Petty (1960) were also unable to produce transplantation immunity in mice after the insertion of relatively enormous cartilage homografts. The explanation may be that the matrix of cartilage prevents the transplantation antigens of chondrocytes from reaching the tissue fluids of the host in sufficient amounts to evoke transplantation immunity. There is only one published report of the capacity of bone to elicit transplantation immunity, by Chalmers (1959), who transplanted homografts of fresh iliac bone from hooded rats intramuscularly into Wistar rats; three weeks later a skin graft obtained from each donor was applied to the corresponding recipient. The second-set skin homografts underwent an early rejection at five to six days compared with a mean survival time of 109 days for the first-set homografts of skin. Chalmers concluded that homografts of iliac bone will evoke transplantation immunity and that the tissue antigens of iliac bone which evoke immune responses in their hosts have antigens in common with skin. Furthermore, freeze-drying altered the tissue antigens in iliac homografts, because subsequent skin grafts from the same donor did not undergo early rejection but survived slightly longer than the first-set skin homografts; this Chalmers called an “enhancement effect.”