Resource Specialist Program

Abstract

N AUTOIMMUNE MECHANISM has been invoked in a number of dis-A ease states, such as the connective tissue diseases, chronic thyroiditis, hemolytic anemia, etc. This type of mechanism has been suggested by the occurrence in these diseases of hypergammaglobulinemia, a number of circulating factors with the characteristics of autoantibodies, decreased serum complement levels, and the production, in some instances, of similar lesions in experimental animals utilizing immunologic methods. In the case of antigens believed to be sequestered, exemplified by certain antigens of the eye, thyroid gland, and nerve tissue, autoimmune reactivity has been thought to result from a failure of induction of tolerance to these antigens because they were, presumably, not freely available to the reticulo-endothelial system in the embryonic or neonatal state. In the case of readily available antigens, however, the occurrence of autoimmune reaction must assume the emergence of immunologically competent cells capable of reacting with one or more antigens of the host. The appearance of such cells has been ascribed either to a failure of the tolerance mechanism1 or to the appearance of abnormal populations of immunologically competent cells through a process of mutation.2is Regardless of the mechanism whereby such cells might arise in autoimmune disease states, it is possible to study the consequences of their presence by providing the experimental animals with immunologically competent cells known to be capable of reacting with anti-gens of the host. This has been studied intensively in this laboratory during the past 2 years. Our observations indicate that such animals do, in fact, develop changes in a number of organ systems which are strikingly similar to those of human connective tissue disease. A large literature describes the production of the graft versus host reaction, or homologous disease, by injection of immunologically competent cells into newborn animal^,^-^ F1 hybrid~,~~s irradiated animals: and adult animals rendered tolerant by neonatal injection of lymphoid cells.1° Homologous disease has also been induced in adults by repeated injection of large numbers of lymphoid cells.11 Oliner, Schwartz and Dameshek have studied the hemato-logic changes in homologous disease from the point of view of autoimmune disease, commenting on the similarity of the pancytopenia to that of human disease.12