Murine mercury-induced autoimmunity - A model of chemically related autoimmunity in humans

Human exposure to certain compounds or therapeutic drugs can result in the development of an autoimmune syndrome. Mercury (Hg) induced autoimmunity is one of the few animal models in which administration of a chemical induces a specific loss of; tolerance to self-antigens. After receiving subtoxic d oses of Hg or other heavy metals, susceptible mouse strains rapidly develop highly specific antibodies to nucleolar antigens. In addition, these anima ls display a general activation of the immune system, especially pronounced for the Th2 subset and a transient glomerulonephritis with immunoglobulin deposits. Like many human autoimmune diseases, this syndrome is associated with the expression of susceptible major histocompatibility complex (MHC) c lass II genes. In this article, we review the essential features of this mo del, and we discuss the putative mechanisms by which Hg creates such a seve re immune dysfunction.