New Insights into Autoimmune Mechanisms and the Pathogenesis of Insulin-Dependent Diabetes Mellitus

Abstract

Today almost everyone agrees that insulin-dependent diabetes mellitus (IDDM) occurs as the result of specific, immunologically mediated destruction of the insulin-producing beta cells of the islets of Langerhans [1,2]. The immunological pathogenesis of this disease was initially suggested by the presence of a mononuclear cell infiltration of the islets, “insulitis,” in patients who had died within a few days of the clinical onset of IDDM [3,4]. The infiltrating cells have been characterized as T-lymphocytes, most of which were CD8 positive (i. e., cytotoxic T-cells) and some that were CD4 positive (i.e., helper T-cells) [5]. Monoclonal antibodies specific for the interleukin 2 receptor and for HLA (human leukocyte antigen) class II molecules have indicated that these T-cells are activated [5]. Further evidence for the immunological origin of IDDM came from the presence of anti-islet cell antibodies (ICA) in a diabetic’s sera [6] and from the success of immunosuppression in increasing remissions in newly diagnosed patients [7,8].

This research was supported in part by National Institutes of Health grant numbers OK-24021, AI-23963, and CA-44977.