The feasibility of altering the immunogenicity of grafts.
Most attempts to prolong the survival of allografts have involved treatment of the host to impair its capacity to reject them. Early uncritical attempts to treat the graft rather than the host were received with skepticism because of the prevailing belief that the alloantigens on cell surfaces are immutable. However, over the past decade unequivocal evidence has accumulated that the immunogenicity of allografts is susceptible to alteration. Short-term maintenance in vitro of malignant and normal tissue grafts, such as those of the ovary and thyroid. Weakens their susceptibility to rejection. Various agents have been identified which, when applied to tissues or organs in vitro, have a similar effect. Soaking skin in media containing steroids, urethane, thalidomide, antilymphocyte globulin (ALG), and specific alloantibody is also effective. X-irradiation and perfusion of allogeneic dog kidneys with solutions of concanavalin A or of nucleic acid prepared from the future donor or even from indifferent donors or microoorganisms lead to extended survival. There is also equivocal evidence that soaking mouse skin grafts in RNA prepared from unrelated donors causes them to be treated as allogeneic by syngeneic recipients. Skin from animals suffering from certain diseases displays altered immunogenicity. Skin from mice suffering from virus-induced leukemia or lymphocytic choriomeningitis is frequently rejected by syngeneic recipients. By contrast, skin allografts from some cancer patients and from mice bearing certain tumors give evidence of prolonged survival as do grafts from uremic mice. Some treatments of prospective donors, including cytotoxic drugs, ALG, specific alloantisera, hypoxia, and experimentally produced uremia, also extend the lives of allografts. Trophoblast, a fetal epithelial tissue in immediate contact with maternal tissue, represents a natural example of graft adaptation. Despite its origin from precursor cells with normal transplantation properties, trophoblast fails to elicit transplantation immunity and is unaffected by it. Some of the disparate agents or procedures described here probably act by modifying grafts in such a way that they are more likely to evoke "blocking" or enhancing antibodies rather than the usual destructive cellular immunity, and many of them deplete the grafts of immunogenically effective "passenger" leukocytes. Both of these processes contribute to apparent hypoantigenicity.
D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000818:Animals; D000867:Anterior Chamber / Q000601:surgery; D000917:Antibody Formation; D000961:Antilymphocyte Serum / Q000494:pharmacology; D003208:Concanavalin A / Q000494:pharmacology; D004247:DNA / Q000494:pharmacology; D005260:Female; D005976:Glutaral / Q000494:pharmacology; D006801:Humans; D007668:Kidney / Q000528:radiation effects; D008214:Lymphocytes / Q000276:immunology; D009368:Neoplasm Transplantation; D010280:Parathyroid Glands / Q000637:transplantation; D011247:Pregnancy; D012313:RNA / Q000494:pharmacology; D011830:Radiation Effects; D016038:Skin Transplantation; D014181:Transplantation Immunology; D014184:Transplantation, Homologous; D014327:Trophoblasts / Q000276:immunology; D014520:Urethane / Q000494:pharmacology; D014965:X-Rays
D000305:Adrenal Cortex Hormones; D000961:Antilymphocyte Serum; D003208:Concanavalin A; D014520:Urethane; D012313:RNA; D004247:DNA; D005976:Glutaral