Cell mediated immunity to islet cells: lessons from animal studies

As a pathogenic factor of type I (insulin-dependent) diabetes cell mediated immunity to pancreatic islet cells, i.e. lymphocytic insulitis has been studied in mice with spontaneous lupus-like autoimmune disease, in mice with experimentally induced immune dysregulation and in mice treated with multiple low doses of streptozotocin or with alloxan. The following conclusions have been reached: Autoimmunity to B-islet cells requires a disturbed immune system. Autoimmune insulitis requires altered B-islet cells. Cellular immunity to B-islet cells apparently involves two different mechanisms: The intrainsular invasion of single lymphocytes and macrophages and the mostly periinsular/periductular infiltration of large numbers of lymphocytes and macrophages. Some observations indicate a primary role of helper and suppressor T lymphocytes as well as of macrophages in B-islet cell destruction. In this paper an attempt will be made to combine observations on the induction and course of insulitis in several animal models in a general scheme of pathological events. Several conclusions on the mechanism of islet autoimmunity have been reached. At the time being however, these "lessons" must be regarded as hypotheses, which may be helpful in understanding the pathogenesis of human type I diabetes.